自闭症（*）是一类常见的神经发育疾病，主要症状是患者患有严重的社交、行为的功能障碍。有研究认为遗传组成使得一些个体容易患有自闭症，而且还分析了一些与自闭症相关的基因。尽管人类的7号染色体被认为与自闭症的易感性密切相关，但一直没有研究者找到该区域里与自闭症直接相关的基因。现在，来自日本理化学研究所脑科学研究所（**）的研究者却在该区域找到了这样一个基因，发现缺乏CADPS2蛋白的小鼠表现出类似自闭症的症状。
研究文章刊登在3月22日的《the Journal of Clinical Investigation》杂志上，Teiichi Furuichi和同事发现缺乏CADPS2（对应于人类7号染色体易感区上的一个基因）的小鼠，在社会互动方面存在障碍：两只素未谋面的CADPS2缺失的小鼠相互接触的频率，要比两只野生型小鼠明显少得多。同时，这些CADPS2缺失的小鼠还伴有多动（***）症状和缺乏探索新环境的能力，所有这些都是患有自闭症个体的明显特征。
还有一个非常重要的证据，患有自闭症的患者在CADPS2 mRNA上存有异常，而这在与他们亲缘性非常高的健康的亲戚身上却未发现，更进一步地暗示CADPS2的功能异常很可能是自闭症的一个诱因。
部分英文原文：
Published Online March 22, 2007
Online First Publication
Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients
Tetsushi Sadakata1, Miwa Washida1, Yoshimi Iwayama2, Satoshi Shoji1, Yumi Sato1, Takeshi Ohkura3, Ritsuko Katoh-Semba4, Mizuho Nakajima2, Yukiko Sekine1, Mika Tanaka5, Kazuhiko Nakamura6, Yasuhide Iwata6, Kenji J. Tsuchiya6, Norio Mori6, Sevilla D. Detera-Wadleigh7, Hironobu Ichikawa3, Shigeyoshi Itohara8, Takeo Yoshikawa2 and Teiichi Furuichi1
1Laboratory for Molecular Neurogenesis and 2Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan. 3Tokyo Metropolitan Umegaoka Hospital, Tokyo, Japan. 4Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Japan. 5Research Resource Center, RIKEN Brain Science Institute, Saitama, Japan. 6Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan. 7Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, Maryland, USA. 8Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Saitama, Japan.
Address correspondence to: Teiichi Furuichi, Laboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan. Phone: 81-48-467-6079; Fax: 81-48-467-6079; E-mail: tfuruichi@brain.riken.jp .
Received for publication May 9, 2006, and accepted in revised form January 16, 2007.
Autism, characterized by profound impairment in social interactions and communicative skills, is the most common neurodevelopmental disorder, and its underlying molecular mechanisms remain unknown. Ca2+-dependent activator protein for secretion 2 (CADPS2; also known as CAPS2) mediates the exocytosis of dense-core vesicles, and the human CADPS2 is located within the autism susceptibility locus 1 on chromosome 7q. Here we show that Cadps2-knockout mice not only have impaired brain-derived neurotrophic factor release but also show autistic-like cellular and behavioral phenotypes. Moreover, we found an aberrant alternatively spliced CADPS2 mRNA that lacks exon 3 in some autistic patients. Exon 3 was shown to encode the dynactin 1–binding domain and affect axonal CADPS2 protein distribution. Our results suggest that a disturbance in CADPS2-mediated neurotrophin release contributes to autism susceptibility.
