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）我们分析了自闭症患者的促胰液素基因、促胰液素受体（SCRC）基因和胃泌素释放肽受体（GRPR）基因的突变情况。在促胰液素基因分析中，我们发现启动子区域的突变导致基因表达降低，并且在5个基因中发现了错义突变。然而，在104名患者中，由于在对照中发现了这些基因，因此未被确认为自闭症基因，并且在促胰液素治疗应答者的患者中没有检测到致病性突变。 2)制备胰泌素和SCRC基因敲除小鼠。对于胰泌素基因敲除小鼠，将胰泌素基因的4个外显子全部替换为β-半乳糖苷酶和新霉素基因，并制备SCRC基因敲除小鼠的外显子1。建立了敲除小鼠，并通过RT-PCR证实了敲除同源小鼠中SCRC基因的缺失。我们计划对这些基因进行分析。对小鼠进行病理学和生化敲除，增加行为分析。

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）。