Mouse Research Pathology

Genetically altered mice provide superb models of human physiology and disease. They allow us to evaluate the effects of single altered genes in the context the whole organism and provide tremendous insight into gene function. However, they can provide research results that are frequently unexpected, confusing or simply uninformative. The comparative pathologist is required to assess phenotypic impact of single gene alterations on complex molecular pathways. The effects of genetic background and the variability inherent in the gene construct used to create the animals frequently confound this assessment. Finally, findings must be integrated with published information to draw conclusions and design new experiments.

The aim of each phenotyping project is unique, however several common features can usually be identified. In most phenotyping studies, the intention is to not only identify the nature of the lesions, but also to assess how such lesions relate to deviation of normal gene expression and cellular physiology. This review will delineate the approach taken during a typical phenotypic assessment, with particular emphasis on evaluation of embryonic and neurologic phenotypes.