FUNCTION OF MAMMALIAN SINGLE MINDED GENES, SIM1 AND SIM2

哺乳动物单一基因 SIM1 和 SIM2 的功能

• 批准号: 6182659
• 负责人: CHEN-MING FAN
• 金额: $ 21.51万
• 依托单位: CARNEGIE INSTITUTION OF WASHINGTON, D.C.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6182659
• 关键词: Drosophilidae; biochemical evolution; developmental genetics; developmental neurobiology; disease /disorder model; early embryonic stage; gene expression; gene targeting; genetic enhancer element; genetic mapping; genetic promoter element; genetically modified animals; histology; immunocytochemistry; in situ hybridization; laboratory mouse; nucleic acid sequence; phenotype; protein purification; tissue /cell culture

DESCRIPTION (adapted from investigator's abstract): The goal of this proposal is to investigate the function of mammalian Sim1 and Sim2 genes using transgenic mouse models. Sim1 and Sim2 are homologues of the Drosophila sim (singleminded) gene. In the fly, sim plays essential roles in the development of the central nervous system. Preliminary studies of the mouse Sim genes strongly suggest evolutionarily conserved functions. The SIM proteins contain conserved sequence motif termed the PAS domain, which is hared by several environmental sensor proteins such as the Dioxin receptor, the Hypoxia Inducible Factor, the Drosophila circadian rhythm regulator Per, and the B. subtilis sporulation regulator KinA. This information strongly indicated that SIMs may also respond to specific environmental signals via their PAS domains. This proposal includes the following aims: 1) documenting the expression patterns of Sim1 and Sim2 in detail; 2) establishing mouse models lacking Sim1 and Sim2 gene function by homologous recombination and characterizing mutant phenotypes in order to assess the normal function of these genes, and 3) identifying possible small molecule ligands that modulate the function of Sim1 and Sim2. Importantly, the mouse Sim2 gene is located in the syntenic human Down syndrome critical region. Furthermore, mutant mice lacking Sim1 display neurological disorders that may relate to multiple sclerosis. Exploration and identification of possible small ligands that regulate Sim1 and Sim2 function will be the first step towards developing methods to alter their gene activities in vivo.

描述（改编自研究者摘要）：本研究的目的