VALIDATION OF HMGI C AS A DRUG TARGET IN OBESITY

HMGI C 作为肥胖症药物靶标的验证

• 批准号: 2647970
• 负责人: ROLAND A CHOUINARD
• 金额: $ 10.07万
• 依托单位: HMGENE, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-15 至 2000-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2647970
• 关键词: DNA binding protein; adipose tissue; body composition; drug design /synthesis /production; drug screening /evaluation; gene targeting; genetically modified animals; laboratory mouse; leptin; lipid biosynthesis; nonhistone nucleoprotein; obesity

DESCRIPTION (Adapted from the application): It is proposed in this application to test whether the DNA binding protein HMGI-C is involved in the development of obesity in the ob/ob mouse. This will be accomplished by breeding ob/ob mice in which one or both HMGI-C alleles have been disrupted, and assessing the impact of these changes on the development of the obese phenotype and its associated abnormalities. The expected result of decreased obesity will provide support for targeting the HMGI-C gene/protein for anti-obesity drug development. Targeted disruption of the HMGI-C gene has been shown by Dr. Chada to result in the pigmy (pg/pg) mouse, which was initially described as a spontaneous mutant with a 20-fold decrease in body fat. This, and the subsequent observations by Dr. Chada's group that mutations of HMGI-C and HMGI-(Y) are found in human lipomas provide the rationale for the proposed studies. Preliminary data is presented that expression of the HMGI-C and HMGI-(Y) genes are elevated in both ob/ob and db/db mice, and that HMGI-C+/- ob/ob mice (N = 2) have delayed weight gain compared to HMGI-C +/+ ob/ob controls. The ob/ob phenotype is considered to be a good model of human obesity that is due to hyperphagia, so that effects of the absence of HMGI-C in mice may have relevance to human obesity. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

描述（改编自申请）：本申请中提出 为了测试DNA结合蛋白HMGI-C是否参与了 肥胖症的发生率。这将通过培育ob/ob小鼠来实现 其中一个或两个HMGI-C等位基因已被破坏，并评估 这些变化对肥胖表型发展的影响及其 相关异常减少肥胖的预期结果将提供 用于抗肥胖药物的靶向HMGI-C基因/蛋白质的支持物 发展Chada博士已经证明了HMGI-C基因的靶向破坏 从而产生侏儒（pg/pg）小鼠，其最初被描述为 自发突变体，体脂肪减少20倍。这个，还有 Chada博士的研究小组随后观察到，HMGI-C和 HMGI-（Y）在人类脂肪瘤中的发现为提出的 问题研究初步数据显示，HMGI-C和HMGI-C的表达与HMGI-C的表达相关。 在ob/ob和db/db小鼠中，HMGI-C+/-（Y）基因均升高， 与HMGI-C +/+ ob/ob小鼠相比，ob/ob小鼠（N = 2）的体重增加延迟 对照ob/ob表型被认为是人类肥胖的良好模型 这是由于摄食过多，因此小鼠中缺乏HMGI-C影响 可能与人类肥胖有关。 拟议商业应用：不可用