Laboratory Mouse Handbook

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Laboratory Mouse Handbook

Copyright 2010 by the AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE (AALAS). All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without written permission from AALAS. While every effort has been made to ensure the accuracy of information contained herein, the publisher, editor, and contributors are not legally responsible for errors or omissions. Cover design by Noah Babiarz. Printed in the USA. Library of Congress Control Number: 2006907770 ISBN 978-0-9789207-0-8 American Association for Laboratory Animal Science 9190 Crestwyn Hills Drive Memphis, TN 38125-8538 - 901.754.8620 fax 901.753.0046 http://www.aalas.org ii

Table of Contents Table Index.... iv Figure Index.... v Preface.... vi 1: Biology... 1 History...1 Taxonomy...1 Normative Values...1 Nomenclature...4 Genetically Engineered Mice...6 Coat Color Genetics...7 Other Genetic Profiles...9 Web Resources for Mouse Genomics and Proteomics...10 Anatomy and Physiology...12 2: Housing and Care.... 19 Environmental Factors in Rooms Housing Mice...19 Housing...20 Caging...20 Bedding...21 Food...21 Water...22 Environmental Enrichment...22 Sanitation and Disinfection of Caging and Equipment...22 Animal Identification...23 3: Medicine.... 25 Infectious Agents...25 Protecting Mouse Colonies from Infection...25 Eliminating Infection from Mouse Colonies...26 Infectious Agents of Laboratory Mice...27 Non-infectious Diseases...42 4: Research Methods.... 47 Physical Restraint and Handling...47 Restraint Devices...47 Injections...48 Blood Collection...50 Perioperative Care...52 Signs of Pain in the Mouse...52 Selection of Anesthetic and Analgesic Agents...53 Methods of Euthanasia...56 Necropsy...56 Appendix: Regulatory Issues and Information Resources.... 59 Color Plates: Anatomical Illustrations.... 61 iii

Table Index Biology Normative Values Table 1 1. Biology...2 Table 1 2. Hematology...2 Table 1 3. Clinical chemistry...2 Table 1 4. Urinalysis...3 Table 1 5. Embryonic development...3 Table 1 6. Additional reproductive info...3 Nomenclature Table 1 7. Abbreviations for common mouse strains used in hybrids...4 Table 1 8. Strain nomenclature...4 Coat Color Genetics Table 1 9. Original letter designation of coat color alleles...8 Table 1 10. Gene protein product designation of coat color alleles...8 Table 1 11. Additional coat color gene alleles...9 Other Genetic Profiles Table 1 12. Major and minor histocompatibility loci of common strains...9 Table 1 13. Leucocytes in common immunologically dysfunctional strains...9 Anatomy and Physiology Table 1 14. Integumentary system...12 Table 1 15. Gastrointestinal system...12 Table 1 16. Urinary system...12 Table 1 17. Male reproductive system...13 Table 1 18. Female reproductive system...13 Table 1 19. Natural breeding efficiency...14 Table 1 20. Respiratory system...14 Table 1 21. Cardiovascular system...14 Table 1 22 Hematopoietic organs...15 Table 1 23. Endocrine system...15 Table 1 24. Central nervous system...16 Table 1 25. Peripheral nervous system...16 Table 1 26. Special senses...16 Table 1 27. Skeletal system...17 Housing and Care Environmental Factors in Rooms Housing Mice Table 2 1. Guidelines for environmental factors in animal rooms...19 Caging Table 2 2. Autoclave temperatures for common caging materials...20 Table 2 3. Recommended housing density... 20 Medicine Infectious Agents of Laboratory Mice Table 3 1. Viral agents...28 Table 3 2. Bacterial agents...34 Table 3 3. Rickettsial and mycotic infections. 38 Table 3 4. Protozoan parasites...39 Table 3 5. Helminth parasites...40 Table 3 6. Arthropod parasites... 41 Research Injections Table 4 1. Recommended needle sizes, sites, and approx maximum injection volumes...49 Blood Collection Table 4 2. Mouse blood and plasma volumes...51 Table 4 3. Mouse blood collection guidelines by percent of total blood volume...51 Selection of Anesthetic and Analgesic Agents Table 4 4. Sedative and immobilization agents...53 Table 4 5. Anesthetic agents...54 Table 4 6. Analgesic agents...55 Table 4 7. Inhalant anesthetic agents...55 Methods of Euthanasia Table 4 8. Methods of euthanasia...56 Regulatory Issues and Information Resources.... 59 iv

Figure Index Housing and Care Animal Identification Figure 2 1. Scheme for identifying a mouse with ear notches/holes....23 Research Physical Restraint and Handling Figure 4 1. Lifting a mouse by the base of the tail....48 Figure 4 2. Tail restraint of a mouse on a wire bar lid....48 Figure 4 3. One-handed mouse restraint...48 Figure 4 4. Two-handed mouse restraint...48 Injections Figure 4 5. Subcutaneous (SC) injection....49 Figure 4 6. Intramuscular (IM) injection....49 Figure 4 7. Intraperitoneal (IP) injection....49 Figure 4 8. Gavage....50 Figure 4 9. Venipuncture of the lateral tail vein....50 Figure 4 10. Vascular catheters and osmotic pumps...50 Blood Collection Figure 4 11. Venipuncture of the facial vein.. 51 Figure 4 12. Orbital sinus blood collection from an anesthetized mouse....51 Figure 4 13. Lateral saphenous venipuncture of a mouse in a restraint device....51 Figure 4 14. Blood collection from the jugular vein or carotid artery....51 Figure 4 15. Blood collection following tail tip amputation....51 Figure 4 16. Cardiac puncture of an anesthetized mouse....51 Perioperative Care Figure 4 17. A mouse prepared for sterile surgery....52 Figure 4 18. Equipment for induction and maintenance of isoflurane anesthesia....53 Methods of Euthanasia Figure 4 19. CO 2 chamber for rodent euthanasia....56 Anatomical Illustrations Color plate 1. Mouse, 1 d of age....61 Color plate 2. Sexing mice, 5 d of age.......62 Color plate 3. Sexing mice, 11 d of age....63 Color plate 4. Sexing mice, 21 d of age.....64 Color plate 5. Sexing mice, adults....65 Color plate 6. Lacrimal glands and salivary glands....66 Color plate 7. Gastrointestinal system....67 Color plate 8. Gastrointestinal system....68 Color plate 9. Male reproductive system....69 Color plate 10. Female reproductive system....70 Color plate 11. Mammary glands....71 Color plate 12. Cervicothoracic organs....72 Color plate 13. Heart and major blood vessels....73 Color plate 14. Heart....74 Color plate 15. Tail cross-section...75 Color plate 16. Skeletal system....76 v

Preface The use of animals has long been a major part of research in biomedical science. Research animals have allowed scientists to search for new therapies and to elucidate basic biological processes and the mechanisms of diseases. This eagerness of humans to understand and explore living matter and the use of animals in science started long ago; however, prior to 1900, only a few scientists used the species Mus musculus as a research animal whereas today approximately 95% of all laboratory animals are mice and other rodents. By 1901, William Castle, the great-grandfather of mammalian genetics, recognized the potential of mice to test Mendel s theories. Nevertheless, it was not until Clarence Cook Little developed the first inbred mouse strain, DBA, in 1909 that the modern laboratory mouse was born. Since then, a large number of mouse strains have been developed through different breeding schemes and technical advances and researchers now have an unprecedented number of animal models, from Snell s first congenic strains in the 1940s, to the nude mouse in the 1960s and the SCID (severe combined immunodeficiency) mouse in the 1980s. Beginning in the 1980s, genetically engineered mice became available that successfully mimicked human diseases and allowed the study of individual gene function and gene-gene interactions. The accessibility of transgenic and knockout mouse strains revolutionized biomedical research and made the mouse the most extensively used laboratory animal. This also led to the need for reference texts that could provide succinct and comprehensive information about the laboratory mouse. The Scientific Advisory Committee of the American Association of Laboratory Animal Science developed this handbook containing up-to-date data needed by scientists involved in murine research. Additionally, a free course on mouse biomethodology (Working with the Laboratory Mouse) is available online in the Animal Care and Use Library of the AALAS Learning Library (http://www.aalaslearninglibrary.org/). Sylvia Gografe vi

Biology Acknowledgments Scientific Editor Sylvia I Gografe, DVM, PhD, DACLAM Technical Editor Geneviève Fridland, MA, EdD Authors Sanford H Feldman, DVM, PhD, DACLAM Sylvia I Gografe, DVM, PhD, DACLAM Dennis F Kohn, DVM, PhD, DACLAM M Michael Swindle, DVM, DACLAM, DipECLAM Reviewers Ron E Banks, DVM, DACLAM, DACVPM Nicole E Duffee, DVM, PhD Craig S Frisk, DVM, PhD, DACLAM Sherril Green, DVM, PhD, DACVIM Hilton J Klein, VMD, MS, DACLAM, DipECLAM Chris Medina, DVM, DACLAM Daniel D Myers, DVM, MPH Patricia V Turner, DVM, DVSc, DACLAM Illustrations Gheorghe M Constantinescu, DVM, PhD, Drhc Photography Allentown, Inc DURECT Corporation Janet Hoff, LVT, LATG Richard Hughes, LATG M Michael Swindle, DVM, DACLAM, DipECLAM Production Page design: Nicole Brown, MA Production assistance: Amy Tippett vii