Live mice should be carefully examined for both behavioral and physical abnormalities. Most homozygous recessive mutations (m/m) are available with heterozygotes (+/m) or wild-type (+/+) age- and sex-matched controls on the same genetic background (where "m" = the mutant gene being studied, and "+" = the normal, or wildtype, gene). Controls should be examined side by side with mutants as a basis for comparison. Familiarity with the normal phenotype of the background strain is essential in assessing the phenotypic variances of the mutant, and is also important in determining the presence of disease. Many infectious diseases in mice can present as behavioral abnormalities, such as circling or torticollis associated with middle ear infections. If these are evident in both mutant and control mice, it will be important to do infectious disease surveillance studies on the colony. Some mutations have clinical phenotypes that resemble infectious diseases, such as cutaneous scaling (possibly ringworm) or focal loss of hair (alopecia potentially due to ectoparasite infestation). Clinical and diagnostic veterinarians are able to deal with these effectively. Disease issues are beyond the scope of this book and are covered in detail elsewhere.5,8
Mice should be allowed to walk around in their box so that their patterns of behavior can be observed. The mice should constantly explore their environment and be alert and active. They should respond to external stimuli without abnormal reactions. Some inbred strains, like DBA/2J respond to loud noises by developing sudden and sometimes prolonged seizures often ending in death.9 The mouse should have a uniform hair coat that lays flat. Vibrissae, the long hairs around the eyes and muzzle, should be straight and prominent. Ears should be erect and light pink in color for albino mice. Pale white ears in albino mice may suggest the presence of anemia. Eyes should be bilaterally symmetrical and clear. Nails should be short and curved. Incisors are commonly overgrown in many strains (malocclusion of incisors), but this may be part of the phenotype if it is constantly observed in association with a particular mouse mutation. Body openings should be checked to make sure that they are normal and normal secretions or excretions are produced. For example, normal mouse feces are about the size and shape of a rice grain, firm to hard in consistency, and dark brown in color. Perianal matting of feces or light yellow colored feces might indicate the phenotype of inflammatory bowel disease or the presence of any number of intestinal infections.10 Several commonly used inbred strains of mice may have perianal swelling, giving the appearance of extra testicles (3 or 4) due to cysts of the bulbourethral glands.11
The animal identification information should be collected at this point. This includes age (birth date and necropsy day on records), sex, strain, genotype if known, pedigree numbers, animal identification numbers including ear tag or punch (Figure 5.1), or toenail amputation, source (room), body weight, reason for submission, and name of submitting technician or scientist. If the mouse is part of an ongoing study, a special code number for that study should be assigned to keep the records straight. (See Chapter 4, Medical Record Keeping for Project Analysis).
These are starting points. Thorough evaluation of the first mutants in a study will provide guidelines on what to look for more specifically as the study progresses.
Routine collection of biological materials is done as part of physical examinations for humans and domestic animals in sickness or health. The methods are identical for mice but microassays are used. These can be done prospectively, as a routine procedure throughout all studies, or retrospectively, once a series of abnormalities is identified, to follow or define the pathogenesis of the disease. Since mutant mice
FIGURE 5.1 Mouse identification by ear notching.
left ear right ear left ear right ear
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