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The Mouse in Biomedical Research: Normative Biology, Husbandry, and Models

The Mouse in Biomedical Research: Normative Biology, Husbandry, and Models

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The Mouse in Biomedical Research: Normative Biology, Husbandry, and Models

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3,002 pagine
49 ore
Pubblicato:
Dec 15, 2006
ISBN:
9780080469072
Formato:
Libro

Descrizione

Normative Biology, Husbandry, and Models, the third volume in the four volume set, The Mouse in Biomedical Research, encompasses 23 chapters whose contents provide a broad overview on the laboratory mouse’s normative biology, husbandry, and its use as a model in biomedical research. This consists of chapters on behavior, physiology, reproductive physiology, anatomy, endocrinology, hematology, and clinical chemistry. Other chapters cover management, as well as nutrition, gnotobiotics and disease surveillance. There are also individual chapters describing the mouse as a model for the study of aging, eye research, neurodegenerative diseases, convulsive disorders, diabetes, and cardiovascular and skin diseases. Chapters on imaging techniques and the use of the mouse in assays of biological products are also included.
Pubblicato:
Dec 15, 2006
ISBN:
9780080469072
Formato:
Libro

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The Mouse in Biomedical Research - Academic Press

American College of laboratory Animal Medicine Series

THE MOUSE IN BIOMEDICAL RESEARCH

Normative Biology, Husbandry, and Models

James G. Fox

Division of Comparative Medicine, MIT, Cambridge, MA

Stephen W. Barthold

Center for Comparative Medicine, Schools of Medicine and Veterinary Medicine, University of California, Davis, CA

Muriel T. Davisson

The Jackson Laboratory, Bar Harbor, ME

Christian E. Newcomer

Research Animal Resources and Department of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD

Fred W. Quimby

Laboratory Animal Research Center, The Rockefeller University, New York, NY

Abigail L. Smith

School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA

Table of Contents

Cover image

Title page

Copyright

List of Reviewers for Chapters in this Volume

Contributors

Foreword for Volume III

Preface

Normative Biology

Chapter 1: Gross Anatomy

INTRODUCTION

ACKNOWLEDGMENT

Chapter 2: Mouse Physiology

I. CARDIOVASCULAR SYSTEM

II. RESPIRATORY PHYSIOLOGY

III. THE DIGESTIVE SYSTEM

IV. METABOLISM: THE PROBLEM OF SIZE

V. THERMOREGULATION

VI. RENAL PHYSIOLOGY*

VII. WATER REGULATION

ACKNOWLEDGMENTS

Chapter 3: Reproductive Biology of the Laboratory Mouse

I. ONTOGENY OF THE REPRODUCTIVE SYSTEM

II. ORGANIZATION AND FUNCTION OF THE REPRODUCTIVE TRACT

III. MANAGING REPRODUCTION IN MICE

ACKNOWLEDGMENTS

Chapter 4: Endocrinology: Bone as a Target Tissue for Hormonal Regulation

I. OVERVIEW

II. BONE CELLULAR ORGANIZATION AND ACTIVITY

III. HORMONAL ACTIONS ON BONE

H. 1,25-Dihydroxy Vitamin D3 [1,25(OH)2D3]

IV. SUMMARY

Chapter 5: Hematology of the Laboratory Mouse

I. INTRODUCTION

II. GENERAL CONSIDERATIONS FOR MURINE HEMATOLOGY

III. TECHNIQUES IN HEMATOLOGY

IV. ERYTHROCYTES

V. LEUKOCYTES

VI. PLATELETS

VII. HEMOSTASIS

VIII. HEMATOLOGY OF THE MOUSE EMBRYO

IX. HEMATOLOGY OF YOUNG MICE

X. HEMATOLOGY OF AGING MICE

XI. THE ROLE OF THE SPLEEN IN MURINE HEMATOPOIESIS

XII. CONCLUSIONS

ACKNOWLEDGMENTS

Chapter 6: Clinical Chemistry of the Laboratory Mouse

I. INTRODUCTION

II. METHODS OF ANALYSIS AND INSTRUMENTATION

III. SAMPLING

IV. REFERENCE RANGES

V. SPECIFIC TESTS

Management, Techniques, and Husbandry

Chapter 7: Gnotobiotics

I. TERMINOLOGY

II. HISTORICAL HIGHLIGHTS IN GNOTOBIOTICS

III. ISOLATOR TECHNOLOGY

IV. DERIVATION OF GNOTOBIOTIC MICE

V. ASSOCIATING GERMFREE MICE WITH DEFINED FLORA

VI. MONITORING FOR ISOLATOR CONTAMINATION

VII. ASSOCIATION FOR GNOTOBIOTICS

Chapter 8: Management and Design: Breeding Facilities

I. INTRODUCTION

II. FACILITIES FOR BREEDING MICE

III. MICROBIOLOGIC STATUS

IV. ESTABLISHING A BREEDING COLONY

V. GENETIC QUALITY CONTROL

Chapter 9: Design and Management of Research Facilities for Mice

I. INTRODUCTION

II. ARCHITECTURE AND ENGINEERING

III. ENVIRONMENTAL CONTROL AND MONITORING

IV. EQUIPMENT

V. MATERIALS

VI. OPERATIONAL ISSUES

VII. ENVIRONMENTAL ENRICHMENT

VIII. CONCLUSION

Chapter 10: Nutrition

I. INTRODUCTION

II. NUTRIENTS: MEASUREMENT AND REQUIREMENTS

III. CONTAMINANTS IN DIET

IV. LABORATORY TESTING

V. DIET TYPES AND FORMULAS

VI. DIET MANUFACTURE

VII. STORAGE OF DIET

VIII. DECONTAMINATION OF DIET

IX. DIET RESTRICTION

X. INFLUENCE OF DIET ON INFECTIOUS DISEASES AND IMMUNITY

XI. WATER

XII. CONCLUDING COMMENTS

Chapter 11: Health Delivery and Quality Assurance Programs for Mice

I. INTRODUCTION

II. HEALTH CARE PROVISION FOR EXPERIMENTAL MICE

III. QUALITY ASSURANCE (QA) PROGRAMS FOR MICE

IV. INFECTIOUS OUTBREAK SOURCES AND MANAGEMENT

V. LIMITATIONS OF OUR CURRENT KNOWLEDGE AND FUTURE DIRECTIONS

Chapter 12: Environmental and Equipment Monitoring

I. INTRODUCTION

II. MANAGEMENT

III. ENVIRONMENTAL FACTORS

IV. EQUIPMENT AND SYSTEMS

V. FEED AND BEDDING

VI. SANITATION

VII. MONITORING FOR PESTS

VIII. CONCLUSION

Chapter 13: Biomethodology and Surgical Techniques

I. INTRODUCTION

II. HANDLING, IDENTIFICATION, AND RESTRAINT

III. DRUG ADMINISTRATION

IV. COLLECTION OF BIOLOGIC SPECIMENS

V. ANESTHESIA

VI. SURGICAL PROCEDURES

VII. POSTANESTHETIC AND POSTOPERATIVE CARE

VIII. EUTHANASIA

IX. NECROPSY

Chapter 14: In-Vivo Whole-Body Imaging of the Laboratory Mouse

I. INTRODUCTION

II. GENERAL FEATURES

III. ADVANTAGES AND OPPORTUNITIES

IV. DISADVANTAGES AND CHALLENGES

V. LOGISTICAL ASPECTS

VI. X-RAY IMAGING, INCLUDING X-RAY COMPUTED TOMOGRAPHY

VII. ULTRASOUND

VIII. MAGNETIC RESONANCE IMAGING

IX. NUCLEAR IMAGING

X. OPTICAL IMAGING

XI. MULTIMODALITY IMAGING

XII. SUMMARY

ACKNOWLEDGMENTS

Use of Mice in Biomedical Research

Chapter 15: Behavioral Testing

I. BEHAVIORAL PHENOTYPES

II. APPROACHES TO MEASURING BEHAVIOR

III. BEHAVIORAL DOMAINS AND SUBDOMAINS

IV. MEASURING BEHAVIOR

V. PLANNING BEHAVIORAL EXPERIMENTS

VI. CONDUCTING A BEHAVIORAL TEST

VII. SOURCES OF INFORMATION

VIII. CONCLUSIONS AND RECOMMENDATIONS

ACKNOWLEDGMENT

Chapter 16: Cardiovascular Disease: Mouse Models of Atherosclerosis

I. INTRODUCTION

II. MOUSE MODELS OF ATHEROSCLEROSIS

III. MODIFIERS OF ATHEROSCLEROSIS

IV. INDUCTION OF CVD IN ATHEROSCLEROTIC MICE

V. SUMMARY AND PERSPECTIVE

Chapter 17: Convulsive Disorders

I. INTRODUCTION

II. HOMOLOGOUS MOUSE MODELS OF HUMAN EPILEPSY

III. ORPHAN MOUSE MUTANTS

IV. MULTIFACTORIAL EPILEPSY

V. CONCLUSION

ACKNOWLEDGMENTS

Chapter 18: Eye Research

I. INTRODUCTION

II. RELEVANCE OF MICE IN EYE RESEARCH

III. PHENOTYPIC EFFECTS PRODUCED BY STRAIN BACKGROUND AND STOCHASTIC EVENTS

IV. OCULAR ANGIOGENESIS

V. GLAUCOMA MODELS

VI. MOLECULAR MECHANISMS IN RETINAL DEGENERATION

Chapter 19: Genetic Analysis of Rodent Obesity and Diabetes

I. THE OBESITY AND DIABETES CRISIS

II. OBESITY IS INFLUENCED BY MANY GENES

III. MOUSE MODELS OF OBESITY AND DIABETES USED IN GENETIC ANALYSIS

IV. FUTURE DIRECTIONS

Chapter 20: Mouse Models in Aging Research

I. INTRODUCTION

II. AGING, SENESCENCE, AND DISEASE: DEFINITIONS AND APPLICATION TO AGING RESEARCH

III. BASICS OF EXPERIMENTAL DESIGN AND HUSBANDRY IN AGING RESEARCH

IV. EXAMPLES OF GERONTOLOGIC STUDIES AND MOUSE MODELS USED

V. SUMMARY AND CONCLUSIONS

Chapter 21: Mouse Models of Inherited Human Neurodegenerative Disease

I. INTRODUCTION

II. INHERITED DEVELOPMENTAL DEGENERATIONS OF THE MOUSE

III. MOUSE MODELS OF INHERITED HUMAN NEURODEGENERATION

IV. CONCLUSIONS

Chapter 22: Mouse Skin Ectodermal Organs

I. INTRODUCTION

II. HAIR FOLLICLES

III. SEBACEOUS GLANDS

IV. INTERFOLLICULAR SKIN

V. SWEAT GLANDS

VI. NAILS

VII. VOLAR PADS

VIII. MAMMARY GLANDS

IX. CONCLUSION

ACKNOWLEDGMENTS

Chapter 23: Quality Control Testing of Biologics

I. INTRODUCTION

II. OVERVIEW OF MICROBIOLOGIC QUALITY CONTROL

III. PRODUCTION

IV. MICROBIOLOGIC QUALITY CONTROL TESTING

V. NONMICROBIOLOGIC QUALITY CONTROL TESTING

VI. INVESTIGATION OF OUT-OF-SPECIFICATION (OOS) RESULTS

Index

Copyright

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List of Reviewers for Chapters in this Volume

Lee S. Adamson,     University of Toronto, ON, Canada

Verena Affolter,     University of California, Davis, Davis, CA

Melissa Berry,     The Jackson Laboratory, Bar Harbor, ME

Joan Cadillac,     The Jackson Laboratory, Bar Harbor, ME

Rachel Caspi,     National Eye Institute, NIH, Bethesda MD

Nathaniel Collins,     Schering Plough Research Institute, Kenilworth, NJ

Jacqueline Crawley,     National Institute of Mental Health, NIH, Bethesda, MD

Wim Crusio,     Laboratoire de Neurosciences Cognitives, France

N. Thomas Ferraro,     University of Pennsylvania School of Medicine, Philadelphia, PA

Jeffrey Friedman,     The Rockefeller University, New York, NY

James Geistfeld,     Taconic Farms Inc., Germantown, NY

Dan Goldowitz,     University of Tennessee, Memphis, TN

Peter Gorelick,     National Cancer Institute, Bethesda, MD

Myron Hinsdale,     Oklahoma Medical Research Foundation, Oklahoma City, OK

R. Lynn Jackson,     Biogen Idec, Inc., Cambridge, MA

Holly Jordan,     Glaxo Smith Kline, N. Carolina

Bruce Lamb,     Case Western Reserve University, Cleveland, OH

George Martin,     University of Washington, Seattle, WA

Roger Orcutt,     St. Jude Children’s Research Hospital, Memphis, TN

Scott Perkins,     Tufts-New England Medical Center, Boston, MA

J. Clifford Rosen,     The Jackson Laboratory, Bar Harbor, ME

J. Robert Russell,     Harlan, Indianapolis, IN

Elyse Schauwecker,     Keck School of Medicine, USC School of Pharmacy, Los Angeles, CA

R. William Shek,     Charles River Laboratories, Inc., Wilmington, MA

Karen Timm,     Oregon State University, Corvallis, OR

Julie Watson,     Johns Hopkins University, Baltimore, MD

T. Mark Whary,     Massachusetts Institute of Technology, Cambridge, MA

Luther Young,     The Jackson Laboratory, Bar Harbor, ME

Rong Yuan,     The Jackson Laboratory, Bar Harbor, ME

Pat Zanzonico,     Memorial Sloan-Kettering Cancer Center, New York, NY

Contributors

Margaret Batchelder,     Bristol-Myers-Squibb Pharmacology, Research Institute, Wallingford, CT 06492

Wesley G. Beamer,     The Jackson Laboratories, Bar Harbor, ME 04609-1500

Erin C. Bridgeford,     Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139

Simon R. Cherry,     Department of Biomedical Engineering, Center for Molecular and Genomic Imaging, University of California at Davis, Davis, CA 95616

Sally Chiu,     Department of Pediatrics, University of California at Davis, Davis, CA 95616

Cheng-Ming Chuong,     Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033

John C. Crabbe,     Portland Alcohol Research Center, Virginia Medical Center, and Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239

Terrie L. Cunliffe-Beamer,     Laboratory Animal Research, Genetics Institute/Wyeth, Andover, MA 01810

Joanne M. Currer,     The Jackson Laboratory, Bar Harbor, ME 04609-1500

Muriel T. Davisson,     The Jackson Laboratory, Bar Harbor, ME 04609

Rick Deitrich,     Facility Planning Consultant, Synectic Resources, Inc.

Krista M. Delahunty,     The Jackson Laboratories, Bar Harbor, ME 04609-1500

Nancy E. Everds,     DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE 19714-0050

Janis S. Fisler,     Department of Nutrition, University of California at Davis, Davis, CA 95616

Kevin Flurkey,     The Jackson Laboratory, Bar Harbor, ME 04609-1500

Diane J. Gaertner,     University Laboratory Animal Resources, University of Pennsylvania, Philadelphia, PA 19104-6014

Raymond C. Givens,     Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461

D.E. Harrison,     The Jackson Laboratory, Bar Harbor, ME 04609-1500

James V. Hawkins,     Laboratory of Animal Medicine & Surgery, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892

Alison M. Hayward,     Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139

Karl Herrup,     Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854

Robert F. Hoyt, Jr.,     Laboratory of Animal Medicine and Surgery, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892

Courtnye N. Jackson,     Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02319

Simon W.M. John,     The Jackson Laboratory, Bar Harbor, ME 04609-1500

Mary J. Kennett,     Animal Research Program, Centralized Biological Laboratory, Pennsylvania State University, University Park, PA 16802

Vladimír Komárek,     Sidlistni 212, Prague, Czech Republic

Laura B. Lemke,     Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02319

Neil S. Lipman,     Research Animal Resource Center Memorial Sloan-Kettering Cancer Center New York, NY 10021

Richard H. Luong,     The Animal Medical Center of New York Department of Pathology New York, NY 10021-8314

Nobuyo Maeda,     Department of Pathology & Laboratory Medicine University of North Carolina at Chapel Hill, Chapel Hill, NC 27599

Robert P. Marini,     Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02319

Patsy M. Nishina,     The Jackson Laboratory, Bar Harbor, ME 04609-1500

Glen Otto,     Animal Research Center, University of Texas, Austin, TX 78712

Maksim V. Plikus,     Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033

Kathleen R. Pritchett,     Charles River Laboratories France, Domaine des Oncins, l’Arbresle CEDEX, France BP 0109

Fred W. Quimby,     Laboratory Animal Research Center, The Rockefeller University, New York, NY 10021

Richard J. Rahija,     Animal Resources Center, St. Jude Children’s Research Hospital, Memphis, TN 38105-2794

Robert L. Reddick,     Department of Pathology, University of Texas Health Services Center, San Antonio, TX 78284

Robert J. Russell,     Harlan, Indianapolis, IN 46229-1706

Mark B. St Claire,     National Institute of Diabetes & Digestive &, Kidney Diseases, National Institutes of Health, Bethesda, MD 20892

Thomas N. Seyfried,     Biology Department, Boston College, Chestnut Hill, MA 02167

William R. Shek,     Charles River Laboratories, Wilmington, MA 01887

J. David Small,     Cary, NC 27513

Richard S. Smith,     The Jackson Laboratory, Bar Harbor, ME 04609-1500

Karla A. Stevens,     Harlan, Indianapolis, IN 46229-0176

John P. Sundberg,     The Jackson Laboratory, Bar Harbor, ME 04609-1500

Robert A. Taft,     The Jackson Laboratory, Bar Harbor, ME 04609-1500

Elizabeth J. Theve,     Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02319

Graham Tobin,     Harlan Teklad, Oxon, UK OX25 1TP

Mariana T. Todorova,     Biology Department, Boston College, Chestnut Hill, MA 02167

Douglas Wahlsten,     Department of Biological Sciences and Great Lakes Institute, University of Windsor, Windsor, ON, Canada N9B 3P4

Craig H. Warden,     Rowe Program in Human Genetics, University of California at Davis, Davis, CA 95616

William J. White,     Charles River Laboratories, Wilmington, MA 01887

Johann Zwaan,     University of Texas Health Sciences, Center at San Antonio, San Antonio, TX 78229

Foreword for Volume III

It is a distinct honor and privilege to write a Foreword for one of the four volumes in the second edition of The Mouse in Biomedical Research. The development and application of genetically altered mice by egg injection or stem-cell knockout technology has resulted in an enormous increase in the number of mice at most biomedical research, testing, and teaching organizations. The following quotation provides a more specific example of the major transformation in the use of experimental mice since the initial edition of the books in 1983: Translational research, in which knowledge derived from molecular and cellular biology is being applied in studies involving systems and integrative biology, is burgeoning (NRC. 2004. National Needs … Biomedical Research. Washington, DC, National Academy Press). The explosion of information in fundamental areas and current research needs make the demands different from those described in the initial volume on the topic. The senior editor of the series, Jim Fox, utilized his persuasive personality and experience as an author and editor to recruit assistant editors and a distinguished panel of chapter contributors not only to update the previous edition but to expand the content. This book and the three others in the series provide a current information base for laboratory animal specialists and biomedical scientists, and the texts for graduate courses on the basic biology of the mouse and its application in model development and translational research.

The 23 chapters are organized into three sections. The six chapters in the first section, Normative Biology, all have new authors. In-Vivo Whole-Body Imaging of the Laboratory Mouse is a new chapter in the second section, Management, Techniques, and Husbandry, and six of the seven other chapters in this section have new authors. The nine chapters in the third section, Use of Mice in Biomedical Research, for example, Mouse Models in Aging Research, are all new.

In this era of whole animal studies (aka integrative biology) and functional genomics, Volume III and the other volumes in the second edition of The Mouse in Biomedical Research are the jewels in the crown of the books sponsored by the American College of Laboratory Animal Medicine.

I want to take this opportunity to acknowledge the prior contribution of the editors of the first edition, Henry L. Foster, J. David Small, and James G. Fox, and to express appreciation to Lucy Wilhelm for her overall coordination of the second edition; her efforts were instrumental in bringing this volume to fruition in a timely manner. It truly represents a labor of love for everyone involved!

GERALD VAN HOOSIER, D.V.M.,     CHAIR, ACLAM PUBLICATIONS COMMITTEE

Preface

The American College of Laboratory Animal Medicine (ACLAM) was formed in 1957 in response to the need for specialists in laboratory animal medicine. The college has promoted high standards for laboratory animal medicine by providing a structured framework to achieve certification for professional competency and by stressing the need for scientific inquiry and exchange via progressive continuing education programs. The first edition of The Mouse in Biomedical Research consisting of four volumes, and published in 1981-1983 was a part of the College’s effort to fulfill those goals. It is one of a series of comprehensive texts on laboratory animals developed by ACLAM over the past three decades: The Biology of the Laboratory Rabbit was published in 1974, The Biology of The Guinea Pig in 1976 and a two-volume work Biology of The Laboratory Rat in 1979 and 1980. Also, in 1979 the College published a two-volume text on Spontaneous Animal Models of Human Disease. In 1984 the first edition of Laboratory Animal Medicine appeared in print followed by Laboratory Hamsters in 1987. The second edition of The Biology of the Laboratory Rabbit was published in 1994. A two-volume treatise on Nonhuman Primates in Biomedical Research was published in 1995 and 1998. A text Anesthesia and Analgesia in Laboratory Animals was published in 1997 followed by the second edition of Laboratory Animal Medicine in 2002. Most recently, the second edition of The Laboratory Rat was published in 2005.

The estimated annual use of 100 million-plus mice worldwide attests to the importance of the mouse in experimental research. The introduction of genetically engineered mice has only increased the usefulness of the mouse model in biomedical research. In no other species of animal has such a wealth of experimental data been utilized for scientific pursuits. Knowledge of the mouse that has been accumulated is, for the most part, scattered throughout a multitude of journals, monographs and symposia. It has been 25 years since the publication of the first edition of the Mouse in Biomedical Research. The intent of this second edition is to build upon the framework of the first edition, rather than simply to update and duplicate the earlier effort.

The intended purpose of this text is to assemble established scientific data emphasizing recent information on the biology and use of the laboratory mouse. Separation of the material into multiple volumes was essential because of the number of subject areas covered. The four volumes consist of 80 chapters coauthored by 167 scientists.

The information in Volume 1 serves as a primer for scientists new to the field of mouse research. It provides information about the history, basic biology and genomics of the laboratory mouse (Mus musculus), as well as basic information on maintenance and use of mouse stocks. Mouse origins and relationships are covered in chapters on history, evolutionary taxonomy and wild mice. Genetics and genomics of the mouse are covered in chapters on genetic nomenclature, gene mapping, cytogenetics and the molecular organization of the mouse genome. Maintenance of laboratory mice is described in chapters on breeding systems for various types of strains and stocks and genetic monitoring. Use of the mouse as a model system for basic biomedical research is described in chapters on chemical mutagenesis, gene trapping, gene therapy, pharmacogenetics and embryo manipulation.

Volume 2 entitled Diseases departs from the first edition of the same title by discussing specific disease-causing microorganisms, whereas the first edition discussed infectious diseases affecting specific organs and tissues. This volume consists of 26 chapters subdivided into RNA viruses and DNA viruses, as well as bacterial, mycotic and parasitic infections. These chapters not only provide updates on pathogenesis, epidemiology and prevention of previously recognized murine pathogens, but also include chapters on newly recognized disease-causing organisms: mouse parvovirus, cilia-associated respiratory bacilli and Helicobacter spp. A separate category, consisting of 3 chapters, discusses zoonoses, tumor pathology of genetically engineered mice and spontaneous diseases in commonly used mouse strains.

Volume 3 encompasses 23 chapters whose contents provide a broad overview on the laboratory mouse’s normative biology, husbandry and its use as a model in biomedical research. This consists of chapters on behavior, physiology, reproductive physiology, anatomy, endocrinology, hematology and clinical chemistry. Other chapters cover management, as well as nutrition, gnotobiotics and disease surveillance. Individual chapters describe the mouse as a model for the study of aging, eye research, neurodegenerative diseases, convulsive disorders, diabetes and cardiovascular and skin diseases. Chapters on imaging, surgical and other research techniques and the use of the mouse in assays of biological products also are included.

Normative Biology

Chapter 1

Gross Anatomy

Vladimír Komárek

I. Introduction

Acknowledgment

References

INTRODUCTION

This chapter presents illustrations likely to be of practical importance to those working with laboratory mice. They include the body regions, a simple demonstration of the skeleton, the muscles, and a dissection of the body cavities with description of major organs. More detailed information is provided in publications by Cook (1965), Hummel et al. (1975), Feldman and Seely (1988), Popesko et al. (1990), and Iwaki et al. (2001). The terminology used here is based on the international veterinary anatomical nomenclature published by Schaller, Constantinescu, Habel, Sack, Simoens, Vos (1992). In the figure captions, XY denotes male and XX female.

ACKNOWLEDGMENT

With her kind consent, the figures presenting the myology and most of those presenting the splanchnology were drawn following the concept of Professor Dr Viera Rajtova (Popesko et al. 1990).

Fig. 1-1 The regions of the body, (regiones corporis), lateral view.

Regions of the face (regiones faciei)

1.

regio dorsalis nasi

2.

regio lateralis nasi

3.

regio naris et apex nasi

4.

regio oralis

5.

regio mentalis

6.

regio buccalis

7.

regio mandibularis

8.

regio intermandibularis

9.

regio orbitalis

10.

regio infraorbitalis

11.

regio zygomatica

12.

regio articulationis temporomandibularis

13.

regio masseterica

Regions of the skull (regiones cranii)

14.

regio frontalis

15.

regio parietalis

16.

regio occipitalis

17.

regio supraorbitalis

18.

regio temporalis

19.

regio auricularis et auricula

Regions of the neck (regiones colli)

20.

regio parotidea

21.

regio subhyoidea

22.

regio colli dorsalis

23.

regio colli ventralis

24.

regio trachealis

Regions of the chest (regiones pectoris)

25.

regio presternalis

26.

regio sternalis

27.

regio mammaria thoracica (see Figure 1-4)

28.

regio costalis

29.

regio scapularis

30.

arcus costalis

Regions of the cranial abdomen (regiones abdominis craniales)

31.

regio hypochondriaca

32.

regio xiphoidea

Regions of the middle abdomen (regiones abdominis mediae)

33.

regio abdominis lateralis

34.

regio umbilicalis

35.

regio plicae lateris

36.

regio mammaria abdominalis (see Figure 1-4)

Regions of the caudal abdomen (regiones abdominis caudales)

37.

regio inguinalis

38.

regio pubica a) scrotalis et b) preputialis in XY et orifitium urethrae externum

39.

regio mammaria inguinalis (see Figure 1-4)

Regions of the back (regiones dorsi)

40.

regio vertebralis thoracis

41.

regio interscapularis

42.

regio lumbalis

Regions of the pelvis (regiones pelvis)

43.

regio sacralis

44.

regio tuberis coxae

45.

regio glutea

46.

regio clunis

47.

regio tuberis ischiadici

48.

regio radicis caudae

49.

regio corporis caudae

50.

regio apicis caudae

51.

regio perinealis

52.

regio analis

53.

regio vulvae

54.

regio clitoridis et orifitium urethrae externum

Regions of the forelimb (regiones membri thoracici)

55.

regio articulationis humeri

56.

regio axillaris

57.

regio brachii

58.

regio tricipitalis

59.

regio olecrani

60.

regio cubiti

61.

regio antebrachii (cranialis, lateralis, caudalis, medialis)

62.

regio carpi (cranialis, lateralis, caudalis, medialis)

63.

regio manus (metacarpi et digiti, cranialis, lateralis, palmaris, medialis)

Regions of the hindlimb (regiones membri pelvini)

64.

regio articulationis coxae

65.

regio femoris (cranialis, lateralis, caudalis, medialis)

66.

regio genus

67.

regio cruris (cranialis, lateralis, caudalis, medialis)

68.

regio tarsi (cranialis, lateralis, caudalis, medialis)

69.

regio pedis (metatarsi et digiti, dorsalis, lateralis, plantaris, medialis)

Fig. 1-2 The regions of the body (regiones corporis), ventral view XY. (For labeling see Fig. 1-1)

Fig. 1-3 The regions of the body (regiones corporis), ventral view XX. (For labeling see Fig. 1-1)

Fig. 1-4 The mammary gland (XX).

1.

pars cervicalis

2.

pars thoracica cranialis 27. regio mammaria thoracica

3.

pars thoracica caudalis 27. regio mammaria thoracica

4.

pars abdominalis 36. regio mammaria abdominalis

5.

pars inguinalis 39. regio mammaria inguinalis

6.

clitoris et orificium urethrae externum

7.

introitus vaginae

8.

anus

9.

papillae mammae

10.

lymphonodus subiliacus

11.

vena epigastrica cranialis superficialis

Fig. 1-5 The skeleton.

1.

skeleton capitis

2.

vertebrae cervicales (7)

3.

vertebrae thoracicae (about 13, 12–14)

4.

vertebrae lumbales (5–7)

5.

vertebrae sacrales (3–4)

6.

vertebrae caudales (about 28, 27–30)

7.

scapula

8.

clavicula

9.

humerus

10.

radius

11.

ulna

12.

ossa carpi

13.

ossa metacarpi

14.

phalanges digitorum

15.

os ilium

16.

os ischii

17.

os pubis (15, 16, and 17 considered to form innominate bone of the pelvic girdle)

18.

femur

19.

patella

20.

tibia

21.

fibula

22.

calcaneus et ossa tarsi

23.

ossa metatarsi

24.

phalanges digitorum

25.

sternum

ViIII. vertebra inflexa III sive vertebra anticlinalis

Fig. 1-6 The muscles of the body (m, musculus).

1.

m. sphincter colli superficialis

2.

m. trapezius, pars cervicalis

3.

m. trapezius, pars thoracica

4.

m. cleidocephalicus

5.

m. sternooccipitalis

6.

glandula lacrimalis extraorbitalis

7.

m. parotidoauricularis et glandula parotis

8.

pars scapularis musculi deltoidei

9.

m. teres major

10.

m. triceps brachii

11.

m. latissimus dorsi

12.

m. serratus ventralis

13.

and 14. pars abdominalis m. pectoralis majoris

15.

fascia thoracolumbalis

16.

m. obliquus externus abdominis

17.

m. gluteus superficialis

18.

m. rectus femoris – m. quadriceps

19.

m. biceps femoris

Fig. 1-7 and 1-8 The muscles of the head.

1.

m. levator nasolabialis

2.

m. levator labii superioris proprius

3.

m. buccinatorius, pars buccalis

4.

m. zygomaticus

5.

m. depressor labii inferioris

6.

m. digastricus, venter rostralis

7.

m. digastricus, venter caudalis

8.

m. masseter, pars profunda

9.

m. masseter, pars superficialis

10.

m. buccinatorius, pars molaris

11.

m. temporalis

12.

m. sternooccipitalis

13.

m. cleidooccipitalis

14.

m. sternohyoideus

15.

m. trapezius, pars cervicalis

16.

m. parotidoauricularis

17.

glandula lacrimalis extraorbitalis et eius ductus

18.

glandula parotis

19.

glandula mandibularis

20.

ductus parotideus

Fig. 1-9 The muscles of the forelimb, lateral view.

1.

clavicula

2.

m. cleidocephalicus

3.

m. cleidobrachialis

4.

m. trapezius, pars cervicalis

5.

m. trapezius, pars thoracica

6.

m. deltoideus, pars scapularis

7.

m. deltoideus, pars acromialis

8.

m. cutaneus trunci

9.

m. triceps brachii, caput longum

10.

m. triceps brachii, caput laterale

11.

m. infraspinatus

12.

m. biceps brachii

13.

m. extensor carpi radialis longus

14.

m. abductor digiti I. (pollicis) longus

15.

and 16. m. extensor digitorum communis

17.

m. extensor digitorum lateralis

18.

m. extensor carpi ulnaris

19.

lymphonodus axillaris accessorius II-V digitus secundus, tertius, quartus, quintus

Fig. 1-10 The muscles of the forelimb, medial view.

1.

clavicula

2.

m. cleidocephalicus

3.

m. trapezius, pars cervicalis

4.

m. trapezius, pars thoracica

5.

m. rhomboideus, pars cervicalis

6.

m. rhomboideus, pars thoracica

7.

m. supraspinatus

8.

m. subscapularis

9.

m. teres major

10.

m. latisimus dorsi

11.

m. cutaneus trunci

12.

m. cleidobrachialis

13.

m. pectoralis ascendens

14.

m. biceps brachii

15.

m. triceps brachii, caput mediale

16.

m. triceps brachii, caput longum

17.

m. extensor carpi radialis

18.

m. pronator teres

19.

m. flexor carpi radialis

20.

m. flexor digitorum profundus

21.

m. flexor carpi ulnaris

22.

lymphonodi cervicales superficiales

23.

lymphonodus axillary proprius

I-IV digitus primus, secundus, tertius, quartus

Fig. 1-11 The muscles of the hindlimb, lateral view.

1.

m. gluteus superficialis

2.

m. gluteus medius

3.

m. tensor fasciae latae, 3′. fascia lata

4.

m. rectus femoris

5.

m. vastus lateralis

6.

m. biceps femoris, 6′. fascia cruris

7.

m. adductor

8.

m. semimembranosus

9.

m. semitendinosus

10.

caput laterale musculi gastrocnemii, 10′. tendo musculi tricipitis surae

11.

m. flexor digiti I, (hallucis) longus

12.

m. extensor digitorum lateralis

13.

m. extensor digitorum longus

14.

tendo musculi peronei longi

15.

m. tibialis cranialis

II-V digitus secundus, tertius, quartus, quintus

Fig. 1-12 The muscles of the hindlimb, medial view.

1.

m. lumbosacrocaudalis dorsalis lateralis

2.

musculi intertransversarii

3.

m. lumbosacrocaudalis ventralis lateralis

4.

m. coccygeus dorsalis

5.

m. coccygeus ventralis

6.

m. obturator externus, pars intrapelvina

7.

m. psoas minor

8.

m. psoas major

9.

m. tensor fasciae latae

10.

m. rectus femoris

11.

m. pectineus

12.

m. vastus medialis

13.

m. adductor

14.

m. gracilis

15.

m. semimembranosus

16.

m. semitendinosus

17.

caput mediale musculi gastrocnemii

18.

m. tibialis caudalis

19.

m. flexor digiti I. (hallucis) longus

20.

m. flexor digitorum longus et tibia

21.

insertio musculi sartorii

22.

tibia

I-IV digitus primus, secundus, tertius, quartus

Fig. 1-13 The brain. A, dorsal view. B, ventral view. C, midline section.

1.

bulbus olfactorius

2.

hemispherium cerebri

3.

gl. pinealis

4.

colliculi rostrales (tectum mesencephali)

5.

colliculi caudales (tectum mesencephali)

6.

cerebellum

7.

medulla oblongata

8.

medulla spinalis

9.

cortex telencephali

10.

hypothalamus

11.

pons

12.

hypophysis (gl. pituitaria)

I

n. (nervus) olfactorius (termination in the bulbus)

II

n. opticus

III

n. oculomotorius

IV

n. trochlearis

V

n. trigeminus

VI

n. abducens

VII

n. facialis

VIII

n. vestibulocochlearis

IX

n. glossopharyngeus

X

n. vagus

XI

n. accesorius

XII

n. hypoglossus

Fig. 1-14 Glands of the neck.

1.

glandula mandibularis

2.

glandula parotis

3.

pars cervicalis thymi

4.

glandula sublingualis

5.

lymphonodi mandibulares

6.

lymphonodus retropharyngeus lateralis

7.

m. digastricus

8.

m. masseter

9.

m. sternohyoideus et m. sternothyroideus

Fig. 1-15 The heart. A, left lateral view, branching of the aorta. B, right lateral view, branching of the vena cava cranialis dextra. C, left lateral view of the thorax.

1.

ventriculus sinister

2.

ventriculus dexter

3.

auricula sinistra

4.

auricula dextra

5.

vena cava caudalis

6.

vena cava cranialis sinistra

7.

vena cava cranialis dextra

8.

arcus aortae

9.

truncus pulmonalis

10.

ligamentum arteriosum

11.

venae pulmonales

12.

truncus brachiocephalicus

13.

arteria subclavia sinistra

14.

arteria carotis communis sinistra

15.

arteria carotis communis dextra

16.

arteria subclavia dextra

17.

arteria thoracica interna sinistra

18.

ramus thymicus sinister

19.

arteria cervicalis superficialis sinistra

20.

arteria vertebralis sinistra

21.

arteria vertebralis dextra

22.

arteria cervicalis superficialis dextra

23.

ramus thymicus dexter

24.

arteria thoracica interna dextra

25.

vena azygos sinistra

26.

vena subclavia dextra

27.

vena jugularis externa dextra

28.

vena thymica dextra

29.

vena thoracica interna dextra

30.

vena jugularis interna dextra

31.

vena cervicalis superficialis dextra

32.

arteria intercostalis suprema

33.

a. c v. intercostales dorsal

34.

cupula diaphragmatis

35.

costa ultima

Fig. 1-16 The ventral view into the radix pulmonis with the heart and lungs removed to demonstrate nerves and ganglia (according to Iwaki, Yamashita, Hayskawa, 2001).

1.

arcus aortae

2.

truncus brachiocephalicus

3.

a. carotis communis sinistra et n. laryngeus recurens sinister

4.

a. subclavia sinistra

5.

a. subclavia dextra

6.

a. axillaris dextra

7.

a carotis communis dextra et n. vagus dexter

8.

esophagus et nervus vagus sinister

9.

trachea et n. laryngeus recurrens dexter

10 -10′.

pars cervicalis trunci sympathici dextri et sinistri

11-11′.

n. phrenicus dexter et sinister

12-12′.

pars thorcica trunci sympathici dextri et sinistri

13.

a. pulmonalis dextra et sinistra

14-14′.

a. vertebralis dextra et sinistra

15-15′.

a. cervicalis superfitialis dextra et sinistra

16-16′.

ganglion stellatum (cervicothoracicum) dextrum et sinistrum

17-17′.

ansa subclavia dextra et sinistra

18.

ramus communicans cum nervo sympathico

19-19′.

ramus cardiacus n. vagi dextri et sinistri

20.

ramus thymicus dexter (artery)

21-21′.

v. cava cranialis dextra et ramus cardiacus trunci sympathici dextri; v. cava cranialis sinistra

22.

ganglia cardiaca

23.

plexus pulmonalis

24.

rami pulmonales n. vagi dextri et ganglia v. pulmonalis dextrae

25.

ramu v. pulmonalis sinistra et ganglia v. pulmonalis sinistrae

26.

ganglion venae cavae cranialis sinistrae

27.

In. mediastinalis cranialis dexter

Fig. 1-17 Dorsal view in to the radix pulmonum (according to Honjin, 1954)

1-1′.

a. carotis communis sinistra et n. vagus sinister; a. carotis communis dextra et n. vagus dexter

2-2′.

n. laryngeus recurrens sinister et dexter et trachea

3-3′.

a. vertebralis sinistra et pars cervicalis trunci sympathici sinistri; pars cranialis trunci sympathici dextri et a. vertebralis dextra

4.

arcus aortae et ramus ad ansa subclavia

5-5′.

a. subclavia sinistra et dextra

6-6′.

a. cervicalis superficialis sinistra et. n. phrenicus sinister; a. cervicalis superficialis dextra et n. phrenicus dexter

7-7′.

ganglion (stellatum) cervicothoracicum sinistrum et a. axillaris sinistra; ganglion (stellatum) cervicothoracicum dextrum et a. axillaris dextra

8-8′.

ramus thymicus sinister et dexter (artery)

9-9′.

a. thoracica interna sinistra et dextra

10-10′.

v. cava cranialis sinistra et ramus cardiacus sinister; v. cava cranialis dextra et ramus cardiacus dexter

11.

ramus communicans ni. vagi dextri cum n. sympathico

12.

plexus trachealis

13.

rami cardiaci nervorum vagorum

14-14′.

a. pulmonalis sinistra et dextra; r. pulmonales nervorum vagorum

15.

v. cava caudalis et ramus communicans inter nervos vagos

16-16′.

rami pulmonales nervorum vagorum

17.

esophagus et n. vagus dexter

18-20.

cor

18-18′.

auricula sinistra et dextra

19.

ventriculus sinister

20.

ventriculus dexter

21.

v. pulmonalis sinistra

Fig. 1-18 Organa cavi thoracis, caudal and ventral view.

1.

trachea et truncus brachiocephalicus

2.

v. cava cranialis et nervus phrenicus sinister

3.

cor in pericardii

4.

pericardium

5.

plica v. cavae caudalis

6.

mediastinum caudale

7.

esophagus et truncus vagi ventralis

8.

truncus vagi dorsalis et aorta

9.

lobus cranialis pulmonis dextri

10.

lobus medialis pulmonis dextri

11.

lobus accessorius pulmonis dextri

12.

lobus caudalis pulmonis dextri

13.

pulmo sinister

14.

v. cava caudalis et n. phrenicus dexter

15.

insertio pleurae

Fig. 1-19 The lung, lateral (costal) view.

Fig. 1-20 The lung, medial (mediastinal) view.

1.

trachea

2.

margo obtusus

3.

margo acutus

4.

margo basalis

5.

pulmo sinister

6.

lobus cranialis pulmonis dextri

7.

lobus medius pulmonis dextri

8.

lobus caudalis pulmonis dextri

9.

lobus accessorius pulmonis dextri

10.

incisura cardiaca

11.

fissura interlobaris

12.

bronchus principalis dexter et rami arteriae et venae pulmonalis

13.

bronchus principalis sinister

14.

rami arteriae et venae pulmonalis

15.

ligamentum pulmonale

Fig. 1-21 The caudal view in the cupula diaphragmatis.

1.

m. psoas major

2.

ureter sinister et v. renalis sinistra

3.

aorta abdominalis et v. cava caudalis

4.

ren sinister

5.

ren dexter

6.

hepar-lobus dexter lateralis

7.

lobus dexter medialis

8.

lobus sinister medialis

9.

lobus caudatus

10.

gaster (ventriculus)

11.

duodenum

12.

lien

13.

corpus pancreatis

14.

lobus pancreatis sinister

15.

lobus pancreatis dexter

16.

omentum majus

17.

mesoduodenum

Fig. 1-22 The digestive tract.

1.

lingua

2.

pars cervicalis esophagei

3.

pars thoracica esophagei

4.

pars abdominalis esophagei et lymphonodi gastrici

5.

pars cardiaca ventriculi (saccus cecus, forestomach)

6.

pars fundica et pylorica ventriculi (glandular stomach)

7.

pars descendens duodeni

8.

pars ascendens duodeni et pancreas

9.

jejunum

10.

lymphonodus pancreaticuduodenalis

11.

lymphonodus jejunalis

12.

ileum

13.

corpus ceci

14.

apex ceci

15.

ampulla coli

16.

colon ascendens

17.

colon transversum

18.

colon descendens

19.

rectum

20.

lymphonodi colici

21.

lymphonodus ileocolicus

22.

sacculus rotundus

Fig. 1-23 The abdominal situs viscerum ventral view.

1.

gaster

2.

duodenum ascendens

3.

jejunum

4.

apex ceci

5.

corpus ceci

6.

ampulla coli

7.

colon ascendens

8.

vesica urinaria et ligamenta

9.

lobus sinister hepatis lateralis, 9′. lobus sinister hepatis medialis, 9″. lobus dexter hepatis medialis, 9″′. lobus dexter hepatis lateralis

10.

vesica fellea

11.

lien

Fig. 1-24 The liver.

A, facies diaphragmatica. B, facies visceralis.

1.

lobus sinister lateralis hepatis

2.

lobus sinister medialis hepatis

3.

lobus dexter medialis hepatis

4.

lobus dexter lateralis hepatis

5.

lobus caudatus hepatis, 5′. processus papillaris hepatis

6.

vesica fellea

7.

vena cava caudalis

8.

ligamentum coronarium sinistrum

9.

ligamentum triangulare sinistrum

10.

ligamentum hepatorenale

11.

ligamentum falciforme et ligamentum teres hepatis

12.

impressio esophagica

13.

omentum minus

14.

impressio ventricularis

15.

impressio duodenalis

16.

impressio jejunalis

17.

vena portae, arteria hepatica, ductus choledochus

Fig. 1-25 The stomach.

A, facies visceralis. B, internal view.

1.

oesophagus

2.

curvatura minor

3.

curvatura major

4.

pars cardiaca

5.

saccus cecus ventriculi, fundus ventriculi

5′.

pars epithelium stratificatum squamosum tunicae mucosae

6.

corpus ventriculi

6′.

pars fundica tunicae mucosae

7.

pars cardiaca tunicae mucosae

8.

pars pylorica ventriculae

8′.

pars pylorica tunicae mucosae

9.

pylorus

10.

duodenum

11.

lien

12.

and 13. pancreas

14.

omentum minus

15.

omentum majus

16.

margo plicatus

Fig. 1-26 The kidneys in situ.

1.

ren dexter

2.

ren sinister

3.

glandula adrenalis sinistra

4.

glandula adrenalis dextra (under the stomach)

5.

ureter dexter et lymphonodus lumbalis aorticus dexter

6.

ureter sinister et lymphonodus lumbalis aorticus sinister

7.

vesica urinaria

8.

ligamentum vesicae medianum

9.

vena cava caudalis, aorta abdominalis, arteria mesenterica cranialis

10.

arteria et vena renalis dextra

11.

arteria et vena renalis sinistra, arteria et vena adrenalis sinistra

12.

arteria et vena ovarica dextra (in XX)

13.

arteria et vena ovarica sinistra (in XX)

14.

ramus muscularis dorsalis dexter

15.

ramus muscularis dorsalis sinister

16.

colon descendenst

17.

arteria et vena circumflexa ilium dextra

18.

arteria et vena circumflexa ilium sinistra

19.

vesica fellea

20.

lien

21.

lobus dexter medialis hepatis

22.

lobus sinister medialis hepatis

23.

lobus sinister lateralis hepatis

24.

curvatura major ventriculi

25.

arteriae mesentericae caudales

Fig. 1-27 The male genital organs in situ.

1.

aorta descendens et vena cava caudalis

2.

ren sinister

3.

ureter sinister

4.

rectum et m. sphincter ani externus

5.

glandula vesiculosa

6.

ductus deferens sinister

7.

vesica urinaria

8.

testis sinister

9.

epididymis

10.

glandula bulbourethralis (partim resecta)

11.

diverticulum glandulae bulbourethralis

12.

symphysis pelvina et m. urethralis et radix penis

13.

penis

14.

preputium

15.

glandula preputialis

16.

m. coccygeus

17.

ligamentum vesicae laterale

18.

ligamentum vesicae medianum

19.

a. et v. testicularis

20.

a. et v. ductus deferentis

Fig. 1-28 The male genital organs. A, ventral view. B, dorsal view.

1.

testis dexter

2.

caput epididymidis

3.

cauda epididymidis

4.

ductus deferens dexter

5.

vena testicularis dextra

6.

glandula ampullaris

7.

glandula vesiculosa

8.

pars anterior prostatae (glandula coagulationis)

9.

ureter sinister

10.

vesica urinaria

11.

prostata (pars ventralis), 11′. prostata (pars dorsalis)

12.

pars membranacea urethrae et m. urethralis

13.

m. bulboglandularis

14.

m. ischiocavernosus

15.

glandula bulbourethralis

16.

diverticulum glandulae bulbourethralis

17.

penis

18.

glandula preputialis

19.

glans penis et orifitium urethrae externum

20.

preputium

21.

arteria testicularis sinistra

22.

arteria ductus deferentis sinistra

Fig. 1-29 The female genital organs in situ.

1.

aorta abdominalis et vena cava caudalis

2.

ren sinistra

3.

ovarium sinistrum

4.

tuba uterina sinistra et mesosalpinx sinistrum

5.

cornu uteri sinistrum

6.

ovarium dextrum, 6′. cornu uteri dextrum

7.

cervix uteri

8.

vagina et m. constrictor vulvae

9.

anus et m. sphincter ani externus

10.

clitoris et seccio transversalis clitoridis

11.

vesica urinaria et ligamentum vesicae laterale et ligamentum vesicae medianum

12.

urethra

13.

symphysis pelvina

14.

glandula clitoridis (preputialis feminina)

15.

corpus cavernosum clitoridis

16.

ureter

Fig. 1-30 The female genital organs, ventral view.

1.

ovarium dextrum

2.

tuba uterina dextra

3.

cornu uteri dextrum

4.

cornu uteri sinistrum (partim resectum)

5.

portio vaginalis uteri, cervix

6.

vagina

7.

vestibulum vaginae

8.

clitoris et preputium clitoridis

9.

glandula clitoridis (preputialis feminina)

10.

urethra

11.

vesica urinaria

12.

ligamentum vesicae medianum

13.

ligamentum vesicae laterale dextrum, 13′. ligamentum vesicae laterale sinistrum

14.

and 14′. ureter dexter et sinister

15.

mesovarium

16.

mesometrium

17.

arteria et vena ovarica sinistra

18.

ramus uterinus arteriae et venae uterinus sinistrae

19.

ramus ovaricus arteriae et venae ovaricae sinistrae

Fig. 1-31 The lymph nodes of the head, neck and thorax (In., lymphonodus, Inn., lymphonodi).

1.

In. parotideus

2.

In. mandibularis

3.

Inn. cervicales profundi

4.

Inn. cervicales superficiales

5.

In. axillaris proprius

6.

In. axillaris accessorius

7.

In. mediastinalis cranialis

8.

Inn. tracheobronchiales

9.

Inn. mediastinales medii et pars thoracica thymi

10.

Inn. mediastinales caudales

Fig. 1-32 The lymph nodes of the body.

1.

In. cervicalis profundus caudalis

2.

Inn. mediastinales craniales

3.

In. axillaris proprius

4.

In. axillaris accessorius

5.

In. aorticus

6.

Inn. renales

7.

In. mesentericus caudalis

8.

Inn. lumbales aortici

9.

Inn. iliaci externi

10.

In. iliacus internus

11.

In. subiliacus

12.

In. iliofemoralis

13.

In. inguinalis superficialis

14.

In. popliteus

REFERENCES

Cook, M.J. The anatomy of the laboratory mouse. London: Academic Press, 1965.

Feldman, D.B., Seely, J.C. Necropsy guide: rodents and the rabbit. Boca Raton, FL: CRC Press, 1988.

Hummel, K.P., Richardson, F.L., Fekete, E. Green E.L., Fahey E.U., eds. Biology of the laboratory mouse. 2nd ed. New York:Dover Publications; 1975:247–307.

Iwaki, T., Yamashita, H., Hayakawa, T. A color atlas of sectional anatomy of the mouse. Tokyo: Adthree Publishing Co. Adthree, 2001.

Popesko, P., Rajtova, V., Horak, J. Atlas anatomie malych laboratornych zvierat. Bratislava:Priroda; 1990;Vol. 2. [(English version published by Wolfe Publishing Ltd, London, 1992.)].

Schaller, O., Constantinescu, G.M., Habel, R.E., Sack, W.O., Simoens, P., de Vos, N.R. Illustrated veterinary anatomical nomenclature. Stuttgart: Enke Verlag, 1992.

The Laboratory Mouse Copyright 2004 Elsevier ISBN 0-1233-6425-6 All rights of production in any form reserved.

Chapter 2

Mouse Physiology

Robert F. Hoyt, Jr., James V. Hawkins, Mark B. St Clair and Mary J. Kennett

I. Cardiovascular System

A. Anatomy

1 The Heart

a Atria and Ventricles

b Conduction System

c Coronary Arteries

d Coronary Veins

e Cardiac Myocyte

2 Peripheral Vessels

B. Ex-Vivo Techniques

1 Isolated Heart Prep

C. In-Vivo Techniques

1 Effects of Anesthesia

2 Arterial Blood Pressure

a Noninvasive Methods to Study Arterial Blood Pressure in Mice

1). Tail-Cuff Pressure Measurements

b Invasive Methods to Study Arterial Blood Pressure in Mice

1). Indwelling Fluid-Filled Catheters

2). Radiotelemetry

3). Transducer-Tipped Catheters

3 Electrocardiography

a Mouse Electrocardiogram

b Phenotyping Uses of ECG

4 Murine Heart Rate

5 Exercise Tolerance Assessment

6 Cardiac Output

7 Noninvasive Imaging

a High-Resolution X-Ray Computed Tomography

b Magnetic Resonance Imaging

1). Using MRI with Mice

c Echocardiography

1). Basic Ultrasonic Principles

2). Echocardiography Imaging in Mice

II. Respiratory Physiology

A. Anatomic and Physiologic Functions of the Murine Respiratory Tract

1 Upper Respiratory Tract

a Nasal Cavity

b Pharynx

c Larynx

d Trachea

2 Lower Respiratory Tract

a Lung

b Alveolar Duct and Acini

3 Blood Supply to the Lung

4 Muscles of Respiration

B. Breathing Patterns

C. Lung Volumes and Capacities

D. Assessment of Pulmonary Function

1 Measuring Lung Function in Humans

2 Pulmonary Function Testing in Mice

a Ex-Vivo Techniques for Measuring Lung Function in Mice

1). Contraction of Isolated Airway Segments

2). Pressure-Volume Curves

b In-Vivo Techniques to Assess Lung Function in Mice

1). Invasive Lung Function Measurement in Mice

a). Airway Pressure Measurements

b). Measurement of Pulmonary Resistance and Dynamic Lung Compliance

2). Noninvasive Measurements of Lung Function in Mice

a). Forced Oscillation Technique

b). Barometric Plethysmography

3). Combination In-Vivo Invasive and Noninvasive Technique

c Diffusion Capacity

3 Alveolar Fluid Transport

E. Murine Models of Asthma

III. The Digestive System

A. Introduction

B. Oral Cavity

C. Esophagus

D. Stomach

E. Exocrine Pancreas

F. Liver and Gallbladder

G. Intestine

IV. Metabolism: The Problem of Size

A. Differences in Metabolic Rate

B. Principles of Allometric Scaling

C. Calculating Metabolic Rate Using Size

D. Applications of Allometric Scaling

V. Thermoregulation

A. The Thermoneutrality Zone

B. Adaptation to Cold

C. Adaptation to Heat

D. Fever

E. Effects of Low Oxygen Tension

VI. Renal Physiology

A. Introduction

B. Morphophysiology

C. Mouse Urine

D. Constituents of Mouse Urine

E. Protein Excretion

F. Renal Clearance

G. Response to Diuretics

H. Genetic Renal Abnormalities

VII. Water Regulation

A. Introduction

B. Water Intake

C. Water Loss

D. Water Turnover

E. Water Content

F. General Considerations

Acknowledgements

References

Over the past two decades the laboratory mouse has emerged as the preferred model system for biomedical research. Despite the small size of the mouse, many researchers have turned to mouse models for studying many physiologic processes due to recent advances in science and technology. An important milestone has been the completion of the sequencing of both the mouse (Mouse Genome Sequencing Consortium 2002) and human genomes (Venter et al. 2001). This has resulted in a number of genetic and physical maps of the mouse genome being published that demonstrated a great deal of synteny between the two species. Despite their clear physical differences, genes from humans and mice are approximately 99% identical (Mouse Genome Sequencing Consortium 2002) with approximately 30,000–40,000 human genes having murine counterparts (Grieder and Strandberg 2003). As such, scientists studying a specific gene or genes associated with a disease phenotype in a murine model may now be able to identify a corresponding human gene producing a similar disease entity.

A second important reason for shifting to mouse models has resulted from the enormous technical advances made in the genetic engineering of mice. The emergence of molecular techniques to produce gene mutations in mice has opened nearly unlimited possibilities for studying the physiologic and pathophysiologic role of almost any functional or regulatory protein in the intact animal (Lorenz 2002). By manipulation of the mouse genome it is now possible to generate animal models for studying the consequences of altered gene expression (overexpression, absence, or suppression) of different proteins (e.g., receptors, enzymes) for normal physiology and pathophysiology of nearly every organ system.

In addition to these important advances, considerable progress has been made in the ability to characterize the resulting mouse phenotypes at the tissue, organ, and whole animal level. In recent years, there has been a plethora of articles describing techniques and new methodologies for evaluating function across a wide range of physiologic disciplines, including cardiovascular, pulmonary, renal, behavioral, neurophysiology, and electrophysiology (Doevendans et al. 1998; Gehrmann and Berul 2000; Hoit 2001; Lorenz 2001, 2002; Meneton et al. 2000; Rao and Verkman 2000; Saba et al. 2000).

Today’s researchers and laboratory animal veterinarians face ever increasing demands to keep abreast of the emerging technologies in each of the research disciplines in order to fulfill their responsibilities in appropriate study design, adequate animal protocol review, and animal care and use. The time of change in animal-based research is upon us as scientists proceed from deciphering of the genetic code of a range of animal species to the determination of functions of the genes that are identified with increasing frequency. Many investigators, unfortunately, do not have extensive experience with in-vivo experimentation in the mouse. As such, the veterinarian is often called on to explain, clarify, or recommend aspects of animal care or experimental manipulation to ensure the optimal use of mouse models. In many areas, however, there is a paucity of information about baseline murine physiologic parameters or there is a lack of consensus about measurement guidelines (Rao and Verkman 2000). Over the past several years a number of Web sites have emerged that provide a wide variety of information related to mouse physiology. Table 2-1 provides a list of some of those sites that may be useful to laboratory animal veterinarians and investigators seeking information on mouse physiology. In addition to the specific information displayed on each Web site, there are often valuable links to other Web sites.

TABLE 2-1

LIST OF WEB SITES WITH INFORMATION ON MOUSE PHYSIOLOGY

The purpose of this chapter is to provide a brief overview of current and emerging information on the physiology of the mouse and to identify key references where specific information is located. This chapter focuses on the feasibility and limitations of methods used to study mouse organ physiology emphasizing the cardiovascular, respiratory, digestive, and renal systems. In addition, there are sections that discuss other important areas pertaining to mouse physiology, including allometric scaling related to metabolism, thermoregulation, and water regulation.

I. CARDIOVASCULAR SYSTEM

During the past 15 years enormous strides have been made in characterizing the murine cardiovascular system. This has occurred primarily because of investigator opportunities to use a plethora of genetically engineered animals that have been generated for a specific cardiovascular phenotype. In these animals, a gene of interest, related to a specific physiologic question, is overexpressed, silenced, or deleted. Despite the generation of these new models, little is known about the normal physiology of the mouse or potential differences that may exist between the many strains of mice. The small mouse heart and rapid heart rate (HR), coupled with the limited availability of appropriately scaled physiologic tools and equipment available for this small species, make physiologic assessments challenging. However, the potential new information obtainable from these valuable new animals will greatly enhance the ability to study genetic regulation of the cardiovascular system. The need to accurately characterize murine cardiovascular function is vitally important (Michael et al. 2004).

It is not the intent of this section to cover all of the available approaches in studying cardiovascular physiology in the mouse but rather to provide an overview of each general area of some of these methodologies and where to find additional information. The Cardiovascular Physiology section begins with an overview of the anatomy of the mouse heart, including some of its unique features, such as size, shape, venous supply to the left and right atria, conduction system, coronary artery and vein distributions, cardiomyocytes, and peripheral vessels. This is followed by the two general approaches used to analyze cardiac function in mice: ex-vivo and in-vivo techniques. The discussion of ex-vivo techniques focuses on the importance and utility of the two isolated heart preparations: the Langendorff and the working heart techniques. The next section is dedicated to the in-vivo techniques used to assess cardiac function. There are a number of important methods under this general category that are used to characterize the mouse phenotype including (1) arterial blood pressure (BP), obtained both invasively and noninvasively, (2) electrocardiograms, (3) murine HRs, (4) exercise effects on cardiac function, and (5) cardiac output (CO). This is followed by an overview of three emerging noninvasive imaging modalities being used to help characterize the mouse cardiovascular phenotype. Many of the in-vivo entities require the mouse to be anesthetized. Before we start with a discussion on each of the in-vivo modalities individually, a brief overview of the impact of various anesthetics on murine cardiac function is given.

A. Anatomy

The cardiovascular systems in humans and mice, with the exception of cardiac size, HR, and small variations in the anatomy, are very similar. The mouse heart is about the same size as a pencil eraser, weighs ∼100–200 mg and beats 500–800 times/min. The human heart weighs about 250–300 g and beats an average of 60–70 times/min (Wessels and Sedmera 2003). Because the murine body is parallel to the ground, the mouse heart does not rest on the diaphragm like the human heart and, therefore, has more room to move around within the pericardial cavity. As such, the murine heart has more of an ellipsoidal, rugby ball shape (Wessels and Sedmera 2003).

To gain an appreciation of the challenges encountered with studying the mouse cardiovascular system, consider the following. When compared with a 25-kg dog (e.g., basset hound), the 25-g mouse has significant proportional differences: ∼1000-fold less body weight and heart weight, ∼100-fold less body surface area, and 10-fold less linear dimensions (Michael et al. 2004).

This section briefly covers basic murine anatomy and, when appropriate, comparisons with human cardiovascular anatomy are noted. For more detail on specific areas of the gross anatomy of the mouse, the readers are referred to a number of excellent references (Cook 1965; Cook 1983; Iwaki et al. 2001; Komàrek 2004; Popesko et al. 1992).

1. The Heart

The heart is fundamentally a hollow muscular organ that is primarily responsible for pumping blood with sufficient pressure and volume to perfuse the body’s tissues. It is located in the thoracic cavity and is surrounded by pericardium. Internally, the heart is composed of four chambers and is divided by a muscular septum into a right and left side. The two chambers on the right side of the heart (right atrium and ventricle) are responsible for receiving partially deoxygenated blood from the body and distributing it via the pulmonary trunk to the lungs for gas exchange to occur. The two chambers on the left side of the heart (left atrium and ventricle) are responsible for receiving oxygen-rich blood from the lungs and pumping it out to the body through the aorta. Each atrium serves primarily as a reservoir for blood with only a small amount of pumping action, which assists with ventricular filling. The right and left ventricles are the major pumping chambers for providing blood to the pulmonary and systemic circulations, respectively (Cook 1983; Roger 1999).

There are four valves located within the heart that ensure blood flows in only one direction through the heart: from the atrium to the ventricle and out through its appropriate artery. The two atrioventricular (AV) valves are located between the atrium and the ventricle on both the left and right sides of the heart. Lying between the right atrium and right ventricle is the right AV valve; the left AV valve lies between the left atrium and the left ventricle. The right AV valve (or tricuspid valve) has three distinct leaflets, whereas the left AV valve (also known as the mitral valve or bicuspid valve) has two distinct leaflets.

The primary function of the two AV valves is to prevent the regurgitation of blood from the ventricles to the atrium during ventricular systolic contraction, thereby ensuring blood flows in only one direction. Blood flows from the veins into the right atrium and passes through the tricuspid valve into the right ventricle. Contraction of the right ventricle sends the blood through the pulmonary valve toward the lungs. As the right ventricle contracts, the tricuspid valve closes to prevent regurgitation of blood back into the right atrium. The closing of the tricuspid valve and the other one-way valves creates the heartbeat sound.

The two other valves within the heart are (1) the pulmonary valve, located at the junction of the right ventricle and pulmonary artery trunk and (2) the aortic valve that lies at the junction of the left ventricle and the aorta. These two valves are sometimes referred to as semilunar valves because they consist of three half-moon-shaped valve cusps. The function of the semilunar valves is to prevent regurgitation of blood from the pulmonary trunk and aorta back into the ventricles when the ventricles relax following contraction.

The heart is composed of three layers: (1) inner endocardium, (2) middle myocardium, and (3) outer epicardium or visceral pericardium. The outer surface of the heart is covered by a delicate, thin mesothelium. Immediately below this layer lies the epicardium, a thin layer composed of fibrous connective tissue and small blood and lymphatic vessels (Elwell and Mahler 1999). The murine myocardium is composed of cardiac muscle cells with centrally located nuclei. It has a rich vascular supply composed of thin-walled arterioles, venules, and a well-organized capillary network (Michael et al. 2004). The endocardium is lined with endothelium and is continuous with the intima of the blood vessels entering and leaving the heart (Elwell and Mahler 1999).

At the base of the heart there is a supportive skeleton formed by fibrous connective tissue. The valves between the atria and ventricles (right tricuspid and left bicuspid) are formed by connective tissue, are covered with endocardium, and have a pale, gelatinous appearance (Krinke 2004). Certain mouse strains (DBA/2, C3H, BALB/c, C, A, CBA, CHI, and C3H/HeN) are genetically predisposed to develop spontaneous myocardial calcification (Vargas et al. 1996).

a.: ATRIA AND VENTRICLES A prominent anatomic variation of the heart between humans and mice is found in the venous supply component of the atria. In the human heart the left atrium receives oxygenated blood from four pulmonary veins (Wessels and Sedmera 2003). In the mouse, however, the pulmonary veins join in a pulmonary confluence behind the left atrium, which in turn empties via a single foramen into the dorsal wall of the left atrium (Webb et al. 1996; Wessels and Sedmera 2003). Another anatomical difference in the atrial anatomy between the two species relates to the venous drainage into the right atrium. The mouse has both a left and right anterior vena cava; humans only have the latter (Wessels and Sedmera 2003). During the embryo stage both species have a left and a right anterior vena cava. Postnatally, the left anterior vena cava regresses and becomes nonfunctional in the human. In the mouse, however, the left anterior vena cava remains functional throughout the animal’s life. Together with the right anterior vena cava, the left anterior vena cava delivers blood from the head back to the heart. They both join together with the posterior vena cava to bring the blood into the right atrium (Wessels and Sedmera 2003).

b.: CONDUCTION SYSTEM The anatomy of the conduction system in the mouse is also somewhat different than that in humans. The sinoatrial node in the murine heart is located in the anterior vena cava above its junction with the right atrium, rather than within the atrium itself (Doevendans et al. 1998). Meijler (1985) reported that both humans and mice share a similar configuration of the mammalian AV node-His system from the AV region to the bundle branches. The size of the AV node correspondingly increases with the increase heart size, although not proportionally, when comparing small to large mammals (Doevendans et al. 1998). Although Purkinje cells are not readily apparent in the myocardium of mice on histologic section, there are occasional paler staining modified cells (Purkinje fibers) present in the myocardium, strongly suggesting that the murine impulse-conduction system merges directly with the myocardium (Doevendans et al. 1998; Elwell and Mahler 1999; Lev and Thaemert 1973).

c.: CORONARY ARTERIES The heart muscle receives a rich blood supply from the coronary arteries, which branch from the aorta just distal to the aortic valve. Identifying the coronary artery system in mice is more difficult than in other species and much about in-vivo coronary artery circulation is still largely unknown (Gan et al. 2004). Rather than appear as prominent structures at or on the surface of the epicardium, the coronary arteries are embedded within the myocardium and generally require an intense light source and magnification to visualize (see Figure 2-1A). Coronary artery anatomy in the mouse is generally felt to be comparable to that of other mammals, with early branching of a large septal artery (also seen in hamsters and rabbits) from the left coronary system (Doevendans et al. 1998). The diameter of the mouse coronary arteries at their ostia (located ∼2 mm from the aortic valve) averages 0.16 mm (Thuroff et al. 1984). In humans, the diameter of a young adult’s epicardial coronary arteries (right, left anterior descending and left circumflex) averages 3.7 mm (Leung et al. 1991). The left coronary artery generally divides into a major septal branch and the left anterior descending (LAD) coronary artery. This latter vessel supplies blood

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