Objective: Few scientists truly understand how to systematically work up laboratory mice that carry spontaneous or genetically engineered mutations. We present our routine approach to initiate these studies.
Methods: A minimum of 2 females and 2 males, both mutant and controls, at birth, weaning, puberty, and maturity are euthanized by CO2 asphyxiation and complete necropsies of all organ systems are performed. To follow skin and hair follicle development, the same groups are taken every 3 days of life for up to 40 days of age but only skin and hair are collected. Skin collected from the dorsal and ventral surfaces, muzzle, ear, tail, and footpads provides information on the major hair follicle and epidermal types. To make sure there is uniformity, tissues should be collected from the same anatomic site from each mouse by the same person. Hairs can be plucked and mounted on glass slides for examination by white and polarized light. Scanning electron microscopy of selected hair samples from affected mice and age and gender matched controls demonstrates structural defects which are often associated with low sulfur levels (element analyses done by SEM). An experienced mouse histopathologist is needed for accurate interpretation. Review with an experienced dermatopathologist will accurately compare the mouse model with specific human diseases. Samples collected concurrently for large scale gene array or other advanced technologies will rapidly generate detailed information on the pathophysiology. Results: Accurate diagnoses with correlation to human diseases can be made.
Conclusions: Standardized methods for evaluating novel mutant mouse phenotypes permits comparisons between both mutant mice and the equivalent human disease.