Structure and function of neonatal social communication in a genetic mouse model of autism.
Structure and function of neonatal social communication in a genetic mouse model of autism.
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DOI：
10.1038/mp.2015.190
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发表时间：
2016-09
影响因子：
11
通讯作者：
Hiroi N
中科院分区：
文献类型：
--
作者：
Takahashi T;Okabe S;Broin PÓ;Nishi A;Ye K;Beckert MV;Izumi T;Machida A;Kang G;Abe S;Pena JL;Golden A;Kikusui T;Hiroi N
了解自闭症谱系障碍（ASD）的关键一步是识别遗传和环境风险因素。一些罕见的拷贝数变异（CNV）已经成为ASD的强大遗传风险因素，但并非所有CNV携带者都表现出ASD，并且ASD症状的严重程度在CNV携带者之间存在差异。虽然有证据表明，各种环境因素调节症状的严重程度，这些因素决定ASD的最终严重程度的确切机制仍然知之甚少。在这里，使用Tbx 1（22q11.2 CNV中编码的基因）杂合的小鼠，我们证明了发声中的遗传触发的新生儿表型在小狗-母亲的社会交流中产生了一个负的环境循环。野生型幼犬单独使用不同的序列的简单和复杂的呼叫类型，但杂合子幼犬单独使用不变的呼叫序列与不太复杂的呼叫类型。当回放时，代表性的野生型呼叫序列引起了母亲的方法，但杂合呼叫序列是无效的。当代表性的野生型呼叫序列被随机化时，它们在引发强烈的母性接近行为方面是无效的。这些数据表明，ASD风险基因改变了其携带者的新生儿呼叫序列，而这种幼崽表型反过来又通过非典型的社会交流减少了母亲的照顾。因此，ASD风险基因通过非典型的新生儿呼叫序列诱导低于最佳的孕产妇护理作为一个负面的新生儿环境因素。
A critical step toward understanding autism spectrum disorder (ASD) is to identify both genetic and environmental risk factors. A number of rare copy number variants (CNVs) have emerged as robust genetic risk factors for ASD, but not all CNV carriers exhibit ASD and the severity of ASD symptoms varies among CNV carriers. Although evidence exists that various environmental factors modulate symptomatic severity, the precise mechanisms by which these factors determine the ultimate severity of ASD are still poorly understood. Here, using a mouse heterozygous for Tbx1 (a gene encoded in 22q11.2 CNV), we demonstrate that a genetically-triggered neonatal phenotype in vocalization generates a negative environmental loop in pup-mother social communication. Wild-type pups used individually diverse sequences of simple and complicated call types, but heterozygous pups used individually invariable call sequences with less complicated call types. When played back, representative wild-type call sequences elicited maternal approach, but heterozygous call sequences were ineffective. When the representative wild-type call sequences were randomized, they were ineffective in eliciting vigorous maternal approach behavior. These data demonstrate that an ASD risk gene alters the neonatal call sequence of its carriers and this pup phenotype in turn diminishes maternal care through atypical social communication. Thus, an ASD risk gene induces, through atypical neonatal call sequences, less than optimal maternal care as a negative neonatal environmental factor.