One of the most common organs to study is the skin. It is relatively easy to examine and identify phenotypic variations which can become an important resource for gene-targeting studies. When evaluating the skin and coat, it is important to keep in mind that phenotypes can vary dramatically. Some mutations have no obvious effects, whereas others can dramatically change the appearance of the mice. Problems with the skin and coat can be due to environmental problems, parasites, autoimmune disease, nutritional disorders, or can be secondary to certain treatments or genetic changes.16 Signs to watch for include dryness, scaling, alopecia, wounds, dermatitis, piloerection, matting, and excessive oiliness to the coat. It is important to recognize that mice do a lot of grooming to themselves and each other. Barbering is common and should not be confused with alopecia. Barbering appears to be a normal dominance behavior. It is important to keep in mind that mice can respond differently to epidermal injury than other mammals. Thus, there are some species-specific features that should not be misinterpreted pathologically.
General categories of cutaneous disease can be used for characterization studies and for identifying potential allelic mutations. These general categories of cutaneous disease include hair color mutations, eccrine gland defects, sebaceous gland defects, primary scarring disorders of the skin, hair shaft growth and structural defects, noninflammatory skin diseases, inflammatory skin diseases, papillomatous skin diseases, bullous and acantholytic skin diseases, and structural and growth defects in nails.16 These disease processes can be identified and studied by clinical examination, skin biopsy procedures, and pathology techniques already discussed.
General necropsy procedures have already been discussed, but there are some specific techniques to keep in mind when obtaining skin samples. Skin should be collected from the dorsal and ventral trunk, eyelids, ears, muzzle, tail, and footpads.8 For large study groups, skin samples should be obtained from the same location in all individual mice. This allows more effective comparison of individuals in the same and different groups. The orientation of the samples should be consistent. The recommended orientation is parallel to the long axis of the body.45 Once obtained, the skin sample should be laid out flat with the hair side up. The sample should be placed on an unlined index card in a head-to-tail orientation and labeled with orientation and where on the body the sample was obtained.16 Skin can then be fixed for histopathology or frozen for immunofluorescence or other biochemical and molecular studies. The epidermis and associated hair follicles are made of stratified squamous epithelia in which genes are turned on and off during growth and maturation. Thus, mice undergo major changes that may affect the phenotype of a mutation. Some of the most dramatic changes occur in the first 3 weeks of life. Thus, specific studies may warrant collecting samples at 2 to 3 day intervals during the first 3 weeks of life. Multiple biopsies can be collected from the same individual to help reduce the numbers of animals used.16 Scanning electron microscopy can be used for skin punches, plucked hairs, and nails. The samples are carefully collected and placed in a gluteraldehyde solution. The front and rear feet are collected at necropsy by amputating at the carpus or tarsus, and then samples are prepared as above.
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