BEHAVIORAL AND FUNCTIONAL-ANALYSIS OF MOUSE PHENOTYPE - SHIRPA, A PROPOSED PROTOCOL FOR COMPREHENSIVE PHENOTYPE ASSESSMENT

For an understanding of the aberrant biology seen in mouse mutations a nd identification of mon subtle phenotype variation, there is a need f or a full clinical and pathological characterization of the animals. A lthough there has been some use of sophisticated techniques, the major ity of behavioral and functional analyses in mice have been qualitativ e rather than quantitative in nature. There is, however, no comprehens ive routine screening and testing protocol designed to identify and ch aracterize phenotype variation or disorders associated with the mouse genome. We have developed the SHIRPA procedure to characterize the phe notype of mice in three stages. The primary screen utilizes standard m ethods to provide a behavioral and functional profile by observational assessment. The secondary screen involves a comprehensive behavioral assessment battery and pathological analysis. These protocols provide the framework for a general phenotype assessment that is suitable for a wide range of applications, including the characterization of sponta neous and induced mutants, the analysis of transgenic and gene-targete d phenotypes, and the definition of variation between strains. The ter tiary screening stage described is tailored to the assessment of exist ing or potential models of neurological disease, as well as the assess ment of phenotypic variability that may be the result of unknown genet ic influences. SHIRPA utilizes standardized protocols for behavioral a nd functional assessment that provide a sensitive measure for quantify ing phenotype expression in the mouse. These paradigms can be refined to test the function of specific neural pathways, which will, in turn, contribute to a greater understanding of neurological disorders.