USE OF MOUSE CHIMERAS TO TEST GENE FUNCTION

DESCRIPTION (provided by applicant): This proposal is written in response to NIMH topic "F. Genetic and Transgenic Technology (subtopic 7): "Innovative technologies to study gene function and expression" listed in the 2001 Omnibus Solicitation for SBIR/STTR grants. 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 genetic effects on complex phenotypes like behavior. The fineness of cell mixing in different chimeric brain regions of wild-type mice will be evaluated. This will permit an assessment of how closely cells of different genotype can interact in chimeric brain tissue. Secondly, the feasibility of methodically limiting the contribution of one of the embryos in aggregates to bias cell proportions across a series of chimeras will be tested. This will be technically advantageous for studying how a minority of mutant cells, for example, function against a background of normal cells, or vice versa. Large-scale chimera analysis has the potential to contribute substantially to the analysis of many different mouse mutant phenotypes, including important mouse models of human function and dysfunction.