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

在这项研究中，我们通过对Gasc1突变小鼠进行综合行为测试，确定了编码组蛋白去甲基化酶的Gasc1基因是自闭症谱系障碍(ASD)的一个新的易感基因。Gasc1突变小鼠表现出过度活跃和刻板印象的行为，以及重现人类ASD症状的工作记忆和参考记忆缺陷。哌酸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是一种经常伴随ASD的发育障碍。哌醋甲酯恢复了突变小鼠的多动行为，这表明人类患者和这个突变小鼠系有类似的发病机制。这些结果提出了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一个有用的动物模型。

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.