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- - ~a~ !.. mu_ ~F~_ _115 ~ _ ~ ~ 1 . ~ : _ ~ _ ~ _ ~ _ _ ~ _ _ l _ _~ it_ At: _ _ _ _ _ 1 1B 51111 ~ _ _ __ ~ _ ~ _' Committee on Dogs Institute of Laboratory Animal Resources Commission on Life Sciences National Research Council NATIONAL ACADEMY PRESS Washington, D.C. 1994

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National Academy Press 2101 Constitution Avenue, N.W. Washington, D.C. 20418 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, National Academy of Engineering, and Institute of Medicine. The members of the committee responsible for the report were chosen for their special competen- cies and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, National Academy of Engineering, and Institute of Medicine. This study was supported by the U.S. Department of Health and Human Services (DHHS) through contract number NO1-CM-07316 with the Division of Cancer Treatment, National Cancer Institute; the Animal Welfare Information Center, National Agricultural Library, U.S. Department of Agriculture (USDA), through grant number 59-32U4-8-60; and Regulatory En- forcement and Animal Care, Animal and Plant Health Inspection Service, USDA, through grant number 59-32U4-8-60. Additional support was provided by the following members of the Pharmaceutical Manufacturers Association: Berlex Laboratories, Inc., Cedar Knolls, New Jersey; Bristol-Myers Squibb Co., New York, New York; Bristol-Myers Research, Princeton. New Jersey; Burroughs Wellcome Co., Research Triangle Park, North Carolina; Dupont Merck Research & Development, Wilmington, Delaware; Johnson & Johnson, New Brunswick, New Jersey; Marion Merrell Dow Inc., Kansas City, Missouri; Pfizer Inc., Groton, Connecticut; Schering-Plough Research, Bloomfield, New Jersey; SmithKline Beecham Pharmaceuticals, Swedeland, Pennsylvania; and Syntex Research, Palo Alto, California. ILAR's core program is supported by grants from the National Center for Research Resources, National Institutes of Health; National Science Foundation; American Cancer Soci- ety, Inc.; and U.S. Army Medical Research and Development Command, which is the lead agency for combined Department of Defense funding also received from the Human Systems Division, Air Force Systems Command; Armed Forces Radiobiology Research Institute; Uni- formed Services University of the Health Sciences; and U.S. Naval Medical Research and Development Command. Any opinions, findings, and conclusions or recommendations expressed in this publica- tion are those of the committee and do not necessarily reflect the views of DHHS, USDA, or other sponsors, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. government or other sponsor. Library of Congress Cataloging-in-Publication Data Dogs: laboratory animal management / Committee on Dogs, Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council. p. cm. Includes bibliographical references and index. ISBN 0-309-04744-7 1. Dogs as laboratory animals. I. Institute of Laboratory Animal Resources (U.S.). Committee on Dogs. SF407.D6D64 1994 636.7'0885 dc20 94-960 CIP Copyright 1994 by the National Academy of Sciences. All rights reserved. Printed in the United States of America

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COMMITTEE ON DOGS Fred W. Quimby (Chairman), Center for Research Animal Resources, New York State College of Veterinary Medicine, Cornell University, Ithaca, New York Emerson L. Besch, Department of Physiological Sciences, University of Florida College of Veterinary Medicine, Gainesville, Florida Linda C. Cork, Department of Comparative Medicine, Stanford University, Stanford, California Suzanne Hetts, Humane Society of Denver, Denver, Colorado Warren C. Ladiges, Department of Comparative Medicine, University of Washington, Seattle, Washington Richard I. Traystman, Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Hospital, Baltimore, Maryland Staff Dorothy D. Greenhouse, Project Director Amanda E. Hull, Project Assistant Norman Grossblatt, Editor The Institute of Laboratory Animal Resources (ILAR) was founded in 1952 under the auspices of the National Research Council. A component of the Commission on Life Sciences, ILAR serves as a coordinating agency and a national and international resource for compiling and disseminating information on laboratory animals, promoting education, planning and con- ducting conferences and symposia, surveying existing and required facili- ties and resources, upgrading laboratory animal resources, and promoting high-quality, humane care of laboratory animals in the United States.

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CONTRIBUTORS Gregory M. Acland, James A. Baker Institute, Cornell University, Ithaca, New York Judith A. Bell, Marshall Research Animals, North Rose, New York Dwight D. Bowman, New York State College of Veterinary Medicine, Cornell University, Ithaca, New York David P. Brooks, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania Phillip R. Brown, Division of Comparative Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland Robert W. Bull, Michigan State University, East Lansing, Michigan Leland E. Carmichael, James A. Baker Institute, Cornell University, Ithaca, New York 'l. Derrell Clark, Animal Resources, University of Georgia College of Veterinary Medicine, Athens, Georgia Patrick W. Concannon, New York State College of Veterinary Medicine, Cornell University, Ithaca, New York Lawrence G. Carbone, New York State College of Veterinary Medicine, Cornell University, Ithaca, New York Laurel }. Dungan, Department of Comparative Medicine, Medical University of South Carolina, Charleston, South Carolina W. Jean Dodds, Hemopet, Santa Monica, California Robin D. Gleed, New York State College of Veterinary Medicine, Cornell University, Ithaca, New York Arthur S. Hall, Department of Animal Care, Oregon Health Sciences University, Portland, Oregon Margaret S. Landi, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania George Lust, James A. Baker Institute, Cornell University, Ithaca, New York Ronald R. Minor, New York State College of Veterinary Medicine, Cornell University, Ithaca, New York Bruce A. Muggenburg, Inhalation Toxicology Research Institute, Albuquerque, New Mexico Bryan E. Ogden, Department of Animal Care, Oregon Health Sciences University, Portland, Oregon Donald F. Patterson, Section of Medical Genetics, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania Arleigh Reynolds, New York State College of Veterinary Medicine, Cornell University, Ithaca, New York IV

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Robert M. Shull, Department of Pathobiology, University of Tennessee College of Veterinary Medicine, Knoxville, Tennessee Alison C. Smith, Department of Comparative Medicine, Medical University of South Carolina, Charleston, South Carolina Rainer F. Storb, Fred Hutchinson Cancer Research Center, Seattle, Washington M. Michael Swindle, Department of Comparative Medicine, Medical University of South Carolina, Charleston, South Carolina Beth A. Valentine, Department of Pathology, New York State College of Veterinary Medicine, Cornell University, Ithaca, New York David A. Valerio, Hazleton Research Products, Denver, Pennsylvania v

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INSTITUTE OF LABORATORY ANIMAL RESOURCES COUNCIL John L. VandeBerg (Chairman), Southwest Foundation for Biomedical Research, San Antonio, Texas Christian R. Abee, University of South Alabama, Mobile, Alabama if. Derrell Clark, University of Georgia College of Veterinary Medicine, Athens, Georgia Muriel T. Davisson, The Jackson Laboratory, Bar Harbor, Maine Neal L. First, University of Wisconsin, Madison, Wisconsin James W. Glosser, University of California School of Veterinary Medicine, Davis, California Jon W. Gordon, Mt. Sinai School of Medicine, New York, New York John P. Hearn, Wisconsin Regional Primate Research Center, Madison, Wisconsin Margaret Z. '}ones, Michigan State University, East Lansing, Michigan Michael D. Kastello, Merck Sharp & Dohme, Rahway, New Jersey Charles R. McCarthy, Kennedy Institute of Ethics, Georgetown University, Washington, D.C. Richard C. Van Sluyters, University of California School of Optometry, Berkeley, California Peter A. Ward, University of Michigan School of Medicine, Ann Arbor Michigan Staff Eric A. Fischer, Director Vl

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COMMISSION ON LIFE SCIENCES Thomas D. Pollard (Chairman), The Johns Hopkins University School of Medicine, Baltimore, Maryland Bruce N. Ames, University of California, Berkeley, California John C. Bailar III, McGill University, Montreal, Quebec, Canada J. Michael Bishop, University of California Medical Center, San Francisco, California John E. Burris, Marine Biological Laboratory, Woods Hole, Massachusetts Michael T. Clegg, University of California, Riverside, California Glenn A. Crosby, Washington State University, Pullman, Washington Leroy E. Hood, University of Washington, Seattle, Washington, Marian E. Koshland, University of California, Berkeley, California Richard E. Lenski, Michigan State University, East Lansing, Michigan Emil A. Pfitzer, Hoffmann-La Roche Inc., Nutley, New Jersey Malcolm C. Pike, University of Southern California School of Medicine, Los Angeles, California Henry C. Pitot III, University of Wisconsin, Madison, Wisconsin Paul G. Risser, Miami University, Oxford, Ohio Jonathan M. Samet, University of New Mexico School of Medicine, Albuquerque, New Mexico Harold M. Schmeck, Jr., Armonk, New York Carla ]. Shatz, University of California, Berkeley, California Susan S. Taylor, University of California at San Diego, La Jolla, California John L. VandeBerg, Southwest Foundation for Biomedical Research, San Antonio, Texas P. Roy Vagelos, Merck & Co., Whitehouse Station, New Jersey Torsten N. Wiesel, Rockefeller University, New York, New York Staff Paul Gilman, Executive Director . . V11

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The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the further- ance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Bruce M. Alberts is president of the National Academy of Sciences. The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Robert M. White is president of the National Academy of Engineering. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and upon its own initiative to identify issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine. The National Research Council was established by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy's pur- poses of furthering knowledge and advising the federal government. Functioning in accor- dance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and National Academy of Engi- neering in the conduct of their services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Bruce M. Alberts and Dr. Robert M. White are chairman and vice- chairman, respectively, of the National Research Council. . . . V111

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Preface It has been 2 decades since the Institute of Laboratory Animal Re- sources first published Dogs: Standards and Guidelines for the Breeding, Care, and Management of Laboratory Animals (National Academy of Sci- ences, Washington, D.C., 1973~. During that period, great strides have been made in improving care and management techniques, making available specific-pathogen-free and purpose-bred dogs, and identifying dogs with precisely defined genetic disorders. The dog has proved to be "man's best friend," not only because it is considered a companion and family member, but also because its use in research has been associated with many break- through discoveries in human medicine (e.g., the discovery of insulin as a treatment for type I diabetes mellitus). The same period has been characterized by increased public awareness and scrutiny of research funding, occupational health and safety, and animal welfare. New federal and state laws specifically intended to protect re- search animals have been promulgated and regulations established. In addi- tion to presenting information relevant to the care and use of dogs in re- search and making recommendations based on an objective evaluation of that information, it was the committee's intent to incorporate in this report those aspects of canine husbandry embodied in federal law. Federal regula- tions and policies protecting dogs in research are therefore summarized in Chapter 1, which provides information for obtaining copies. Specific de- tails of the regulations and policies are given throughout the text. IX

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x PREFACE The committee firmly believes that good research requires a good ani- mal-care program. The committee is also aware of the tremendous varia- tion in physiologic traits among canine models. Dogs vary greatly in size, age, health status, physical conformation of the breed, behavioral character- istics, and experience. Therefore, no standard of animal care is likely to be optimal for all dogs. The committee recommends that performance stan- dards be used with sound professional judgment in implementing the ani- mal-care program. Readers who detect errors of omission or commission or who have evidence to support improved procedures are invited to send suggestions to ILAR, National Research Council, 2101 Constitution Avenue, Washington, DC 20418. The committee wishes to thank the entire staff of ILAR, but especially Dr. Dorothy Greenhouse and Ms. Amanda Hull, for assisting in the produc- tion of this manuscript. The committee also acknowledges the many fine contributions made to this report by scientists specializing in the care and use of dogs in research; their names appear on pages iv and v. Fred W. Quimby, Chairman Committee on Dogs

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Contents 1 INTRODUCTION References 3 CRITERIA FOR SELECTING EXPERIMENTAL ANIMALS Genetic Factors 5 Biologic Factors 7 Behavioral Factors 7 Hazards 9 References 3 HUSBANDRY Housing 1 2 Exercise and Environmental Enrichment 21 Food 24 Water 26 Bedding and Resting Apparatuses 26 Sanitation 27 Identification and Records 27 Emergency, Weekend, and Holiday Care 29 Transportation 39 References 32 Xl 11

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. . All 4 MANAGEMENT OF BREEDING COLONIES Reproduction 35 Neonatal Care 40 Reproductive Problems 41 Special Nutritional Requirements 42 Vaccination and Deworming 43 Socialization of Pups 44 Record Keeping 46 References 47 VETERINARY CARE Procurement 52 Control of Infectious Diseases 53 Control of Parasitic Diseases 57 Recognition and Alleviation of Pain and Distress 63 Surgery and Postsurgical Care 68 Euthanasia 70 References 72 6 SPECIAL CONSIDERATIONS Protocol Review 76 Restraint 78 Special Care for Animal Models 78 Aging 79 Cardiovascular Diseases 81 Ehlers-Danlos Syndrome 91 Endocrinologic Diseases 93 Hematologic Disorders 97 Immunologic Diseases 101 Lysosomal Storage Diseases 107 Muscular Dystrophy 110 Neurologic Disorders 112 Ophthalmologic Disorders 114 Orthopedic Disorders 116 Radiation Injury 117 Gene Therapy 119 References 122 APPENDIX: CROSS REFERENCE INDEX CONTENTS 35 51 76 131 133

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