Studies on mouse model of autism spectrum disorders with mutation in a novel disease susceptibility gene Gasc1

在这项研究中，我们确定Gasc1基因，编码组蛋白去甲基化酶，作为一个新的易感基因自闭症谱系障碍（ASD）的Gasc1突变小鼠进行全面的行为测试电池。Gasc1突变小鼠表现出过度活跃和刻板的行为，以及工作和参考记忆缺陷，重现了人类ASD症状。哌醋甲酯是治疗注意缺陷多动障碍（ADHD）最常用的精神活性药物，ADHD是一种经常伴有ASD的发育障碍。哌醋甲酯恢复了突变小鼠的多动行为，表明人类患者和这种突变小鼠系具有相似的发病机制。这些结果提高了Gasc1突变引起的异常表观遗传修饰导致发育障碍的可能性，Gasc1突变小鼠为研究包括ASD在内的人类发育障碍提供了有用的动物模型。

In this study we identified Gasc1 gene, which encodes histone demethylating enzyme, as a novel susceptibility gene for autism spectrum disorders(ASD) by subjecting Gasc1 mutant mice to a comprehensive behavioral test battery. The Gasc1 mutant mice showed hyperactive and stereotyped behaviors, and working and reference memory deficits that recapitulated human ASD symptoms. Methylphenidate is the most commonly prescribed psychoactive drug for the treatment of attention deficit hyperactivity disorder(ADHD), a developmental disorder frequently accompanied by ASD. Methylphenidate restored the hyperactive behavior of the mutant mice, suggesting that human patients and this mutant mouse line have a similar pathogenesis. These results raise the possibility that the abnormal epigenetic modifications caused by Gasc1 mutation lead to developmental disorders, and the Gasc1 mutant mice provide a useful animal model to study human developmental disorders including ASD.