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Committee on Rodents
Institute of Laboratory Animal Resources
Commission on Life Sciences
National Research Council
NATIONAL ACADEMY PRESS
Washington, D.C. 1996
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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 competences
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 5932U4-8-59; and Howard Hughes
Medical Institute through grant number 70209-500104. Additional support was provided by
Charles River Laboratories, Wilmington, Massachusetts; Harlan Sprague Dawley, Indianapo-
lis, Indiana; and the following members of the Pharmaceutical Manufacturers Association:
Abbott Laboratories, Abbott Park, Illinois; Amgen, Inc., Thousand Oaks, California; Berlex
Laboratories, Inc., Cedar Knolls,~New Jersey; Bristol-Myers Squibb Co., New York, New
York; Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey; Burroughs
Wellcome Co., Research Triangle Park, North Carolina;' Ciba-Geigy, Summit, New Jersey;
Dupont Merck Research & Development, Wilmington, Delaware; Johnson & Johnson, New
Brunswick, New Jersey; Marion Merrell Dow Inc., Kansas City, Missouri; Pfizer Inc., Groton,
Connecticut; Sandoz Research Institute, East Hanover, New Jersey; Schering-Plough Research,
Bloomfield, New Jersey; SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylva-
nia; Syntex Discovery Research, Palo Alto, California; 3M Corporation, St. Paul, Minnesota;
and Wyeth-Ayerst Research, Philadelphia, Pennsylvania.
Core support is provided to the Institute of Laboratory Animal Resources by the Com-
parative Medicine Program, National Center for Research Resources, National Institutes of
Health, through grant SP40RR0137; the National Science Foundation through grant BIR-9024967;
the U.S. Army Medical Research and Development Command, which serves as the lead agency
for combined U.S. Department of Defense funding also received from the Human Systems
Division of the U.S. Air Force Systems Command, Armed Forces Radiobiology Research
Institute, Uniformed Services University of the Health Sciences, and U.S. Naval Medical
Research and Development Command, through grant DAMD17-93-J-3016; and research project
grant RC-1-34 from the American Cancer Society.
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 sponsors.
Library of Congress Cataloging-in-Publication Data
Rodents / Committee on Rodents, Institute of Laboratory Animal Resources, Commission on
Life Sciences, National Research Council.
p. cm. (Laboratory animal management series)
'February 1996."
Includes bibliographical references and index.
ISBN 0-309-04936-9
1. Rodents as laboratory animals. I. Institue of laboratory Animal Resources (U.S.).
Committee on Rodents.' II. Series. SF407.R6R62 1996
619' .93 dc20 96-4532
Copyright 1996 by the National Academy of Sciences. All rights reserved.
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COMMITTEE ON RODENTS
Bonnie J. Mills (Chairman), Biotech Group, Immunotherapy Division,
Baxter Healthcare Corp., Irvine, California
Anton M. Allen, Laboratory Animal Health Services Division, Micro-
biological Associates, Inc., Rockville, Maryland
Lauretta W. Gerrity, Animal Resource Program, University of Alabama
at Birmingham, Birmingham, Alabama
Joseph J. Knapka, Veterinary Resources Program, National Center for
Research Resources, National Institutes of Health, Bethesda, Maryland
Arthur A. Like, Department of Pathology, University of Massachusetts,
Worcester, Massachusetts
Frank Lilly, Department of Molecular Genetics, Albert Einstein College
of Medicine, Bronx, New York
George M. Martin, Department of Pathology, University of Washington,
Seattle, Washington
Gwendolyn Y. McCormick, Laboratory Animal Resources, Searle,
Skokie, Illinois
Larry E. Mobraeten, The Jackson Laboratory, Bar Harbor, Maine
William J. White, Professional Services, Charles River Laboratories,
Wilmington, Massachusetts
Norman S. Wolf, Department of Pathology, University of Washington,
Seattle, Washington
CONTRIBUTORS
Wallace D. Dawson, Department of Biological Sciences, University of
South Carolina, Columbia, South Carolina
Edward H. Letter, The Jackson Laboratory, Bar Harbor, Maine
Barbara McKnight, Department of Biostatistics, School of Public Health,
University of Washington, Seattle, Washington
Glenn M. Monastersky, Transgenics, Charles River Laboratories,
Wilmington, Massachusetts
Richard J. Traystman, Department of Anesthesiology and Critical Care
Medicine, The Johns Hopkins Hospital, Baltimore, Maryland
Stay
Dorothy D. Greenhouse, Senior Program Officer
Amanda E. Hull, Program Assistant
Norman Grossblatt, Editor
. . .
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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
I. Derrell Clark, University of Georgia, College of Veterinary Medicine,
Athens, Georgia
Muriel T. Davisson, The Jackson Laboratory, Bar Harbor, Maine
Bennett Dyke, Southwest Foundation for Biomedical Research, San
Antonio, Texas
Neal L. First, University of Wisconsin, Madison, Wisconsin
flames W. Glosser, Massillon, Ohio
John P. Hearn, Wisconsin Regional Primate Research Center, Madison.
Wisconsin
Margaret Landi, SmithKline Beecham Pharmaceuticals, King of Prussia,
Pennsylvania
Charles R. McCarthy, Kennedy Institute of Ethics, Georgetown Univer
sity, Washington, D.C.
Roberta. Russell, Harlan Sprague Dawley, Inc., Frederick, Maryland
Richard C. Van Slayters, University of California, School of Optometry,
Berkeley, California
Peter A. Ward, University of Michigan School of Medicine, Ann Arbor,
Michigan
Thomas D. Pollard, The Johns Hopkins University School of Medicine,
Baltimore, Maryland (ex officio member)
Stay
Eric A. Fischer, Director
Thomas L. Wolfle, Program Director
Mara L. Glenshaw, Research Assistant
Carol M. Rozmiarek, Project Assistant
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 develops guidelines and positions
and disseminates information on the scientific, technological, and ethical
use of laboratory animals and related biological resources. ILAR promotes
high-quality, humane care of laboratory animals and the appropriate use of
laboratory animals and alternatives in research, testing, and education. ILAR
serves as an advisor to the federal government, the biomedical research
community, and the public.
IV
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COMMISSION ON LIFE SCIENCES
Thomas D. Pollard (Chairman), The Johns Hopkins University School of
Medicine, Baltimore, Maryland
Frederick R. Anderson, Cadwalader, Wickersharn & Taft, Washington, D.C.
John C. Bailar, III, McGill University, Montreal, Canada
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
Ursula W. Goodenough, Washington University, St. Louis, Missouri
Susan E. Leeman, Boston University School of Medicine, Boston,
Massachusetts
Richard E. Lenski, Michigan State University, East Lansing, Michigan
Thomas E. Lovejoy, Smithsonian Institution, Washington, D.C.
Donald R. Mattison, University of Pittsburgh, Pittsburgh, Pennsylvania
Joseph E. Murray, Wellesley Hills, Massachusetts
Edward E. Penhoet, Chiron Corporation, Emeryville, California
Emil A. Pfitzer, Research Institute for Fragrance Materials, Inc.,
Hackensack, New Jersey
Malcolm C. Pike, University of Southern California School of Medicine,
Los Angeles, California
Henry C. Pitot, III, McArdle Laboratory for Cancer Research, Madison,
Wisconsin
Jonathan M. Samet, The Johns Hopkins University, Baltimore, Maryland
Harold M. Schmeck, Jr., North Chatham, Massachusetts
Carla J. Shatz, University of California, Berkeley, California
John L. VandeBerg, Southwest Foundation for Biomedical Research, San
Antonio, Texas
Stay
Paul Gilman, Executive Director
v
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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. Harold Liebowitz 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 Academv of Sciences bY its congressional charter to be an adviser to the
O
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. Harold Liebowitz are chairman and vice-
chairman, respectively, of the National Research Council.
Vl
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Preface
Biomedical and behavioral research, product testing, and many aspects
of science education rely heavily on the use of animals. Quality care of
these animals is essential, not only for the animals' welfare, but also for
obtaining valid data. Environmental and biologic factors can influence
experimental results by exerting subtle influences on an animal's physi-
ologic characteristics, behavior, or both. Although there is a tendency to
feel more concern for species to which humans develop an attachment (e.g.,
dogs and cats) and species that are biologically "closer" to humans (nonhu-
man primates), the same attention to environmental control for and good
care of every laboratory species is necessary to ensure the high quality of
both science and ethical practice.
Rodents are, by far, the largest group of animals used in research and
testing. In 1986, the Office of Technology Assessment estimated that 17-22
million animals were being used each year in the United States, of which
about 13.2-16.2 million were rodents (Alternatives to Animal Use in Re-
search, Testing, and Education; Pub. No. OTA-BA-273; U.S. Congress Of-
fice of Technology Assessment; Washington, D.C.; 1986~. In the 15 years
since the last Institute of Laboratory Animal Resources report on the gen-
eral management of rodents was published, important advances in biomedi-
cal research and increased public awareness have created a new environ-
ment for animal research. Modern technology- such as insertion of functional
genes from other species into mice or rats, elimination of a single selected
. .
V11
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. . .
V111
PREFACE
gene or function in mice, and the re-creation of elements of the human
immune system in mice has greatly expanded the usefulness of rodents in
drug development and as models of human diseases. The technologic re-
quirements of such advanced systems have led to improved understanding
and implementation of environmental requirements for the care and use of
rodents in research.
The intent of this report is to provide current information to laboratory
animal scientists (including both animal-care technicians and veterinarians),
investigators, research technicians, and administrators on general elements
of rodent care and use that should be considered both for optimal design
and conduct of research and to meet current standards of care and use. We
emphasize that this report provides guidelines and should not be used as a
substitute for good professional judgment, which is essential in the applica-
tion of the guidelines. Where possible, we refer to other documents that
provide more detail on specific aspects of rodent care and use.
Bonnie J. Mills, Chairman
Committee on Rodents
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Contents
1 LABORATORY ANIMALS AND PUBLIC PERSPECTIVE
Regulatory Issues 1
Ethical Considerations 3
References 4
2 RESPONSIBILITIES OF ANIMAL CARE AND USE
COMMITTEES
Program Oversight 6
Protocol Review 7
Personnel Qualifications and Training
Occupational Health and Safety 12
Use of Hazardous Agents 14
References 1 5
3 CRITERIA FOR SELECTING EXPERIMENTAL ANIMALS
Species and Stocks 16
Standardized Nomenclature 21
Quality 27
Selected Aspects of Experimental Design 31
References 33
6
16
4 GENETIC MANAGEMENT OF BREEDING COLONIES 35
Genetically Defined Stocks 35
Nongenetically Defined Stocks 39
IX
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x
Cryopreservation 40
Record-Keeping 42
References 43
HUSBANDRY
Housing 44
Environment 49
Food 58
Water 64
Bedding 65
Sanitation 66
Identification and Records 71
Rodents Other Than Rats and Mice 72
References 76
6 VETERINARY CARE
Preventive Medicine 85
Surveillance, Diagnosis, Treatment, and
Control of Diseases 190
Emergency, Weekend, and Holiday Care 97
Minimization of Pain and Distress 98
Survival Surgery and Postsurgical Care 100
Euthanasia 105
References 107
7 FACILITIES
Location and Design 115
Construction and Architectural Finishes 1 18
Monitoring 1 18
Special Requirements 1 19
Security 1 19
References 1 20
8 RODENTS THAT REQUIRE SPECIAL CONSIDERATION
Immunodeficient Rodents 123
Wild Rodents 128
Aging Cohorts 131
Rodent Models of Insulin-Dependent Diabetes Mellitus 141
Transgenic Mice 148
References 1 54
APPENDIX: SOURCES OF INFORMATION ON IMPORTING
RODENTS
INDEX
CONTENTS
44
85
114
159
161
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