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

1)我们分析了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）基因的突变情况，在分泌素基因分析中，我们发现104例孤独症患者中有5例存在启动子区突变，导致基因表达降低，其中5例存在错义突变。然而，他们没有被证实为自闭症的基因，因为他们被发现在控制。2）建立分泌素基因敲除小鼠和分泌素基因敲除小鼠模型，对分泌素基因敲除小鼠进行β-半乳糖苷酶和新霉素基因的替换，获得分泌素基因敲除小鼠。敲除小鼠被递送。对于SCRC基因敲除小鼠，将外显子1替换为β-半乳糖苷酶和新霉素基因。建立SCRC基因敲除小鼠模型，通过RT-PCR证实敲除小鼠中SCRC基因表达缺失，并对这些小鼠进行病理学和生化学分析，同时进行行为学分析。

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.