Identification for the genes of autism by the analysis of neuronal peptides and linkage analysis.

通过神经元肽分析和连锁分析鉴定自闭症基因。

基本信息

批准号：
14570766
负责人：
YAMAGATA Takanori
金额：
$ 2.18万
依托单位：
Jichi Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570766/
关键词：
Autism secretin secretin receptor MBD1 Knockout mouse FOXP2 セクレチン受容体ノックアウトマウス

项目摘要

1. We have analyzed the genes on 7q where the linkage with autistic disorder has reported, and also the functional candidate genes of autism using DHPLC method and sequencing. We analyzed several genes for mutations on Japanese autistic population and found a SNP on FOXP2 relate to the autistic population. FOXP2 is a gene for dyslexia, therefore it is interesting to know the relation with autism. Addition to that, we detected a base change of C805T that induce R269C on MBD1 in a patient with autistic disorder, and not in the control group. It is suggested that MBD1 relate to autistic disorder. MBD1 belongs to the genes of methylation binding domain with MECP2 and work for the gene silencing.2. We established secretin receptor Knockout (Sctr KO) mouse and analyzed it. Secretin receptor was expressed in the brain, stomack, pancreas, and kidney. In the brain, it was expressed in hypocampus, deep layer of cerebral cortex, amygdala, hypothalamus and cerebellum. On the behavior test, Sctr KO mouse showed the abnormal response on tube test and partition test These result meant that social recognition was impaired in Sctr KO mouse. Abnormality of social behavior is one of the main feature of autism. Sctr Ko mouse also showed the impaired long term potential on hypocampus. These results showed that secretin is working in the brain and relate to autism. Further analysis is expected to elucidate the function of secretin in the brain and relation to autism.

1. 我们利用DHPLC方法和测序分析了7q上已报道与自闭症相关的基因，以及自闭症的功能候选基因。我们分析了日本自闭症人群的几个突变基因，发现 FOXP2 上的一个 SNP 与自闭症人群相关。 FOXP2 是阅读障碍的基因，因此了解它与自闭症的关系很有趣。除此之外，我们在自闭症患者（而非对照组）中检测到 C805T 的碱基变化，该变化会诱导 MBD1 上的 R269C。 MBD1 被认为与自闭症相关。 MBD1属于与MECP2甲基化结合域的基因，起到基因沉默的作用。2．我们建立了促胰液素受体敲除（Sctr KO）小鼠并对其进行了分析。促胰液素受体在脑、胃、胰腺和肾中表达。在大脑中，其表达于下丘脑、大脑皮层深层、杏仁核、下丘脑和小脑。在行为测试中，Sctr KO小鼠在试管测试和分区测试中表现出异常反应。这些结果表明Sctr KO小鼠的社会识别能力受损。社会行为异常是自闭症的主要特征之一。 Sctr Ko 小鼠还显示出海脑回的长期潜力受损。这些结果表明促胰液素在大脑中发挥作用并与自闭症有关。进一步的分析有望阐明促胰液素在大脑中的功能及其与自闭症的关系。