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

1.对已报道的与自闭症相关的基因进行了7q上的基因分析，并对自闭症的功能候选基因进行了DHPLC分析和测序。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与自闭症人群有关。Foxp2是阅读障碍的一个基因，因此了解它与自闭症的关系是很有趣的。此外，我们在自闭症患者的MBD1上检测到了导致R269C的C805T的碱基变化，而在对照组中没有检测到。提示MBD1与自闭症有关。结论：1.MBD1属于与MECP2甲基化结合区基因，起到基因沉默的作用。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、胰腺和肾脏中表达。在大脑中，表达于下丘脑、大脑皮层深层、杏仁核、下丘脑和小脑。在行为学测试中，Sctr KO小鼠在管实验和分割实验中表现出异常反应，这一结果表明Sctr KO小鼠的社会再认功能受损。社会行为异常是自闭症的主要特征之一。SCTRKO小鼠也表现出在下校园的长期潜伏期受损。这些结果表明，分泌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分泌素在大脑中的功能以及与自闭症的关系。

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.