Gobayashi Yuko, Takumi Toru
Hiroshima University School of Medicine, Japan.
Brain Nerve. 2011 Oct;63(10):1111-6.
Substantial evidence suggests that chromosomal abnormalities contribute to the risk of autism. The duplication of human chromosome 15q11-q13 is known to be the most frequent cytogenetic abnormality observed in autism. We replicate this genetic abnormality in mice by using chromosome engineering to generate a 6.3 Mb duplication of the conserved linkage group on mouse chromosome 7. Mice with paternal duplication showed poor social interaction, behavioral inflexibility, abnormal ultrasonic vocalizations, and correlates of anxiety. This chromosome-engineered mouse model for autism seems to replicate various aspects of human autistic phenotypes and validates the relevance of the human chromosomal abnormality. This model will help in understanding the genetics of developmental brain disorders and thereby serve as an invaluable tool for therapeutic development.
大量证据表明，染色体异常会增加患自闭症的风险。已知人类染色体15q11-q13的重复是自闭症中观察到的最常见的细胞遗传学异常。我们通过染色体工程在小鼠中复制这种遗传异常，以产生小鼠7号染色体上保守连锁群的6.3 Mb重复。父本重复的小鼠表现出社交互动不良、行为缺乏灵活性、异常的超声波发声以及焦虑相关症状。这种针对自闭症的染色体工程小鼠模型似乎复制了人类自闭症表型的各个方面，并验证了人类染色体异常的相关性。该模型将有助于理解发育性脑疾病的遗传学，从而成为治疗开发的宝贵工具。
