THE MERCK VETERINARY MANUAL
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Mice and Rats as Laboratory Animals

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Rodents used for research are maintained in tightly controlled environments designed to reduce the impact of unwanted variables in animal experiments (see Laboratory Animals). Many factors have the potential to influence biologic responses or the results of a laboratory test. Research journals often require standardized descriptions of research rodents and their environment in the materials and methods section, as part of the description of the experiment. Environmental conditions, husbandry procedures, and animals must be similar if research data generated from one laboratory is to be compared with data from others. If variables are not properly controlled, results may be of limited use or even useless. One of the most important variables is the effect of infectious agents on research mice and rats.

Few infectious agents found in laboratory mice and rats today cause overt, clinical disease. Critical to interpreting the microbiologic status of laboratory animals is distinguishing between infection and disease. Infection indicates the presence of microorganisms, which may be pathogens, opportunists, or commensals, of which the last two are most numerous. Clinical disease does not need to be present for microorganisms to affect research. Animals that appear normal and healthy may be unsuitable as research subjects due to the unobservable but significant local or systemic effects of viruses, bacteria, and parasites with which they may be infected.

Diagnosis of infections in research rodent colonies is often based on serology, although molecular methods of detection (eg, PCR) are increasingly being used. The laboratories that perform serologic assays primarily test groups of research animals.

Because of the steady increase in awareness of the varied and generally unwanted effects of natural pathogens, greater efforts have been made to exclude pathogens from research animals. Before 1950, original stocks of mice and rats used as research animals harbored a variety of natural, or indigenous, pathogens. Improvements in sanitation, nutrition, environmental control, and other aspects of animal husbandry led to a significant reduction in the range and prevalence of pathogens found in laboratory rodents. The period from 1950–1980 was a period of gnotobiotic derivation, when cesarean rederivation was used to replace infected stock with uninfected offspring. In this procedure, full-term fetuses are removed from an infected dam and transferred to a germ-free environment and foster care. This procedure was successful in eliminating pathogens not transmitted in utero. Since 1980, eradication of indigenous murine viruses has been undertaken. Reduction in infectious agents has been accomplished through serologic testing of animals for antibodies to specific pathogens and subsequent elimination or cesarean rederivation of antibody-positive colonies.

Most modern animal facilities incorporate some form of health monitoring into their animal care program (see Infectious Agents Commonly Tested for in Laboratory RodentsTables). The well-being of the colony is more important than the well-being of an individual animal; laboratory animal medicine is effectively a type of herd medicine. While health monitoring is costly, it results in significant longterm savings in time, effort, and money. Through these programs, research veterinarians can monitor the health status of the colony, inform researchers of the pathogen status of their animals, prevent entry of most pathogens into the facility, and promptly detect and manage pathogens that do enter.

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Last full review/revision July 2011 by Thomas M. Donnelly, BVSc, DACLAM

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