日本广岛大学的一个研究小组在6月26日出版的《细胞》杂志上报告说，他们已成功培育出自闭症模型实验鼠，该成果可帮助专家研究自闭症的致病基因。
自闭症是一种脑发育障碍，患者在社会交往方面有严重障碍。专家以为自闭症的发病与多个基因相关，但是目前尚有很多疑点有待研究。
广岛大学教授内匠透领导的研究小组发现，在自闭症患者特有的基因异常中，出现频率最高的是第15号染色体部分区域的异常重复。他们通过改变实验鼠受精卵的基因，再现了同样的染色体异常。
研究职员用上述转基因受精卵培育出幼鼠并让它们参加各种测试。结果显示，假如上述异常染色体源自雄鼠，则幼鼠有某些自闭症的症状，如对其四周同类的反应会稍显迟钝，且经常不断地重复同一个动作等；但假如这种幼鼠的异常染色体源自雌鼠，则幼鼠的行为与正常实验鼠无大区别。
原始出处：
Cell, Volume 137, Issue 7, 1235-1246 doi:10.1016/j.cell.2009.04.024
Abnormal Behavior in a Chromosome- Engineered Mouse Model for Human 15q11-13 Duplication Seen in Autism
Jin Nakatani1,10,Kota Tamada1,2,10,Fumiyuki Hatanaka1,3,Satoko Ise4,Hisashi Ohta4,Kiyoshi Inoue1,Shozo Tomonaga1,Yasuhito Watanabe1,2,Yeun Jun
Chung5,Ruby Banerjee5,Kazuya Iwamoto6,Tadafumi Kato6,7,Makoto Okazawa1,Kenta Yamauchi8,Koichi Tanda8,Keizo Takao8,9,Tsuyoshi Miyakawa8,9,Allan
Bradley5andToru Takumi1,3,7,,
1 Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan
2 Kyoto University Graduate School of Biostudies, Kyoto University Graduate School of Medicine, Sakyo, Kyoto 606-8501, Japan
3 Department of Molecular Neuroscience, Kyoto University Graduate School of Medicine, Sakyo, Kyoto 606-8501, Japan
4 Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd., Tsukuba, Ibaraki 300-2611, Japan
5 The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
6 Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan
7 Graduate School of Biomedical Sciences, Hiroshima University, Minami, Hiroshima 734-8553, Japan
8 Frontier Technology Center, Kyoto University Graduate School of Medicine, Sakyo, Kyoto 606-8501, Japan
9 Division of Systems Medicine, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan
10 These authors contributed equally to this work
Substantial evidence suggests that chromosomal abnormalities contribute to the risk of autism. The duplication of human chromosome 15q11-13 is known to be the most frequent cytogenetic abnormality in autism. We have modeled this genetic change in mice by using chromosome engineering to generate a 6.3 Mb duplication of the conserved linkage group on mouse chromosome 7. Mice with a paternal duplication display poor social interaction, behavioral inflexibility, abnormal ultrasonic vocalizations, and correlates of anxiety. An increased MBII52 snoRNA within the duplicated region, affecting the serotonin 2c receptor (5-HT2cR), correlates with altered intracellular Ca2+ responses elicited bya 5-HT2cR agonist in neurons of mice with a paternal duplication. This chromosome-engineered mouse model for autism seems to replicate various aspects of human autistic phenotypes and validates the relevance of the human chromosome abnormality. This model will facilitate forward genetics of developmental brain disorders and serve as an invaluable tool for therapeutic development.