Analysis of G-protein coupled receptors as candidate genes for autism

G蛋白偶联受体作为自闭症候选基因的分析

• 批准号: 12670773
• 负责人: YAMAGATA Takanori
• 金额: $ 1.92万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670773/
• 关键词: autism; mutation analysis; secretin; secretin receptor; GRPR; G-protein coupled receptor; Hereditary Multiple Exostosis; EXT1; GRPR; ノックアウトマウス

1) We analyzed secretin gene, secretin receptor (SCRC) gene and gastrin releasing peptide receptor (GRPR) gene for mutation on autism patients.In secretin gene analysis, we found mutations in promoter region that decrease the gene expression, and missense mutations in 5 of 104 patients. However, they were not confirmed as a gene for autism because they were found in control. And there was no secretin gene mutation on the patients of secretin treatment responder.No pathogenic mutation was detected in SCRC and GRPR genes.2) Secretin and SCRC gene knockout mice were developed.For secretin gene knockout mice, all of four exons of secretin gene were replaced with β-galactosidase and neomycine gene. The knockout mice were delivered. For SCRC gene knockout mice, exon 1 was replaced with β-galactosidase and neomycine gene. The knockout mice were established and the absence of SCRC gene expression in knockout homo mice were confirmed by RT-PCR.We are planing to analyze these knockout mice pathologically and biochemically, additon to the behavior analysis.

1)对104例孤独症患者的分泌素基因、分泌素受体(SCRC)基因和胃泌素释放肽受体(GRPR)基因进行突变分析，发现104例患者中有5例发生启动子区域基因突变，导致基因表达下降，并存在错义突变。然而，这些基因没有被确认为自闭症的基因，因为它们是在对照组中发现的。2)建立了分泌素和scrC基因敲除小鼠，对于分泌素基因敲除小鼠，用β-半乳糖苷酶和新霉素基因替换了分泌素基因的全部4个外显子。基因敲除的老鼠被送来了。对于scrc基因敲除小鼠，外显子1被β-半乳糖苷酶和新霉素基因取代。我们建立了基因敲除小鼠，RT-PCR证实基因敲除小鼠中没有SCRC基因的表达，我们计划对这些基因敲除小鼠进行病理和生化分析，并对其进行行为学分析。

项目成果

Yamagata T, Aradhya S, Mori M, Inoue K, Momoi MY, Nelson DL: "The Human Secretin gene : Fine Structure in 11p15.5 and Sequence Variation in Patients with Autism"Genomics. (in press). (2002)

Yamagata T、Aradhya S、Mori M、Inoue K、Momoi MY、Nelson DL：“人类促胰液素基因：11p15.5 的精细结构和自闭症患者的序列变异”基因组学。

Li H, Yamagata T, Mori M, Momoi M: "Association of autism in two patients with hereditary multiple exostoses that is caused by the novel deletion mutations of EXT1"Journal of Human Genetics. (印刷中). (2002)

Li H、Yamagata T、Mori M、Momoi M：“由 EXT1 的新型缺失突变引起的两名遗传性多发性外生骨疣患者的关联”《人类遗传学杂志》（2002 年）。

LiH, Yamagata T, Mon M, Momoi MY: "Association of autism in two patients with hereditary multiple exostoses that is caused by the novel deletion mutations of EXT1"Journal of Human Genetics. (in press). (2002)

LiH、Yamagata T、Mon M、Momoi MY：“两名患有遗传性多发性外生骨疣的患者与自闭症相关，这是由 EXT1 的新型缺失突变引起的”《人类遗传学杂志》。

Li H, Yamagata T, Mori M, Momoi MY: "Association of autism in two patients with hereditary multiple exostoses that is caused by the novel deletion mutations of EXT1"Journal of Human Genetics. (in press). (2002)

Li H、Yamagata T、Mori M、Momoi MY：“两名患有遗传性多发性外生骨疣的患者与由 EXT1 的新型缺失突变引起的自闭症相关”《人类遗传学杂志》。

Yamagata T, Swaroop Aradhya, Mori M, Inoue K, Momoi MY, David L.Nelson: "The Human Secretin gene : Fine Structure in 11p15.5 and Sequence Variation in Patients with Autism"Genomics. (印刷中). (2002)

Yamagata T、Swaroop Aradhya、Mori M、Inoue K、Momoi MY、David L.Nelson：“人类促胰液素基因：11p15.5 的精细结构和自闭症患者的序列变异”基因组学（2002 年出版）。