权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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方法和测序技术对已报道的与孤独症连锁的7q上的基因进行了分析，并对孤独症的功能候选基因进行了分析。我们分析了日本孤独症人群的几个基因突变，发现FOXP2上的SNP与孤独症人群相关。FOXP2是一个阅读障碍的基因，因此了解它与自闭症的关系是很有趣的。除此之外，我们检测到C805T的碱基变化，其在患有自闭症的患者中诱导MBD1上的R269C，而在对照组中没有。提示MBD1与孤独症有关。MBD1与MECP 2属于甲基化结合域基因，对基因沉默起作用.我们建立了分泌素受体基因敲除（Sctr KO）小鼠并对其进行了分析，分泌素受体在脑、胃、胰腺和肾脏中均有表达。在脑组织中，表达于海马、大脑皮质深层、杏仁核、下丘脑和小脑。在行为学测试中，Sctr基因敲除小鼠在试管实验和分区实验中均表现出异常反应，说明Sctr基因敲除小鼠的社会认知功能受损。社会行为异常是孤独症的主要特征之一。Sctr Ko小鼠也表现出海马下长时程电位受损。这些结果表明，分泌素在大脑中起作用，与自闭症有关。进一步的分析有望阐明分泌素在大脑中的功能以及与自闭症的关系。