Use of Mouse Chimeras to Test Gene Function

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The commercial objective of MusWorks Inc. is to provide a mouse aggregation chimera production service to the biomedical research community. Mouse chimeras are genetically composite animals whose cells are derived from different embryos. Chimera analysis is a particularly valuable tool for assessing how mutations affect the cellular interactions that underlie complex biological systems, most notably the formation and function of the brain. We aim to evaluate the feasibility and utility of using large series of chimeras to analyze a variety of genes that have different roles in central nervous system development and function. We will create four series of chimeras incorporating different mouse mutant models: the Clock mutant, prestin knockout mice tamoxifen-inducible CREB-repressor transgenic mice, and a Math1 gene knock-in. In applying chimera analysis to study a variety of neuroscience problems, we will assess, by extension, the value of chimera analysis to biomedical research in general. Large-scale chimera analysis has the potential to contribute substantially to the analysis of mouse mutant phenotypes, including important mouse models of human function and dysfunction.