Use of Mouse Chimeras to Test Gene Function

描述（由申请人提供）：本建议书是为了回应NIMH主题“F。遗传和转基因技术（副主题7）：“研究基因功能和表达的创新技术”，列入2001年SBIR/STTR赠款综合征求。 MusWorks Inc.的商业目标是为生物医学研究界提供小鼠聚集嵌合体生产服务。小鼠嵌合体是基因复合动物，其细胞来自不同的胚胎。嵌合体分析是一种特别有价值的工具，用于评估遗传对复杂表型（如行为）的影响。 将评价野生型小鼠不同嵌合脑区中细胞混合的精细度。这将允许评估不同基因型的细胞在嵌合脑组织中相互作用的密切程度。其次，将测试系统地限制聚集体中的一个胚胎对一系列嵌合体中的偏倚细胞比例的贡献的可行性。这将在技术上有利于研究少数突变细胞如何在正常细胞的背景下发挥作用，反之亦然。大规模的嵌合体分析有可能大大有助于许多不同的小鼠突变表型的分析，包括人类功能和功能障碍的重要小鼠模型。

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.