Use of Mouse Chimeras to Test Gene Function

使用小鼠嵌合体测试基因功能

• 批准号: 6737157
• 负责人: SHARON S LOW
• 金额: $ 53.82万
• 依托单位: MUSWORKS, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-26 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6737157
• 关键词: biotechnology; cell cell interaction; cerebellar ataxia /dyskinesia; circadian rhythms; cochlea; developmental genetics; ethology; gene expression; genetic models; genetically modified animals; genotype; hippocampus; laboratory mouse; mutant; neural degeneration; neurogenetics; neurophysiology; phenotype; proprioception /kinesthesia; suprachiasmatic nucleus; technology /technique development; tissue mosaicism

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.

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，可用于评估突变如何影响复杂生物系统中的细胞相互作用，尤其是大脑的形成和功能。 我们的目的是评估使用大量嵌合体来分析在中枢神经系统发育和功能中具有不同作用的各种基因的可行性和实用性。我们将创建四个系列的嵌合体，其中包含不同的小鼠突变模型：Clock 突变体、prestin 基因敲除小鼠、他莫昔芬诱导的 CREB ​​阻遏物转基因小鼠和 Math1 基因敲入。在应用嵌合体分析来研究各种神经科学问题时，我们将通过扩展评估嵌合体分析对一般生物医学研究的价值。大规模嵌合体分析有可能对小鼠突变表型的分析做出重大贡献，包括人类功能和功能障碍的重要小鼠模型。