Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene
Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene
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DOI：
10.1073/pnas.0503739102
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发表时间：
2005-07-05
影响因子：
11.1
通讯作者：
Buxbaum, JD
中科院分区：
文献类型：
--
作者：
Shu, WG;Cho, JY;Buxbaum, JD
之前已经在KE家族中研究了言语和语言的神经生物学，其中一半的成员在言语和语言方面都有严重的障碍。负责表型的基因被定位到染色体7q31，并确定为FOXP2基因，编码一个转录因子，包含一个多聚谷氨酰胺道和一个叉头DNA结合域。由于连锁研究暗示7q31在自闭症中，其中语言障碍是障碍的一个组成部分，并且在特定的语言障碍中，FOXP2也被认为是自闭症和/或特定语言障碍中语言缺陷的潜在易感性位点。在这项研究中，我们的特点是在小鼠Foxp2基因中断小鼠。Foxp2基因的两个拷贝的破坏导致了严重的运动障碍，过早死亡，以及当幼崽从母亲身边被带走时引起的超声波发声的缺乏。该基因的单个拷贝的破坏会导致适度的发育延迟，但响应于这种分离的超声波发声会发生显着改变。杂合子动物的学习和记忆似乎正常。在Foxp2破坏的小鼠中观察到小脑异常，浦肯野细胞特别受影响。我们的研究结果支持Foxp2在小脑发育中的作用，以及在各种生物体中包含社会交流功能的发育过程中的作用。
Neurobiology of speech and language has previously been studied in the KE family, in which half of the members have severe impairment in both speech and language. The gene responsible for the phenotype was mapped to chromosome 7q31 and identified as the FOXP2 gene, coding for a transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain. Because of linkage studies implicating 7q31 in autism, where language impairment is a component of the disorder, and in specific language impairment, FOXP2 has also been considered as a potential susceptibility locus for the language deficits in autism and/or specific language impairment. In this study, we characterized mice with a disruption in the murine Foxp2 gene. Disruption of both copies of the Foxp2 gene caused severe motor impairment, premature death, and an absence of ultrasonic vocalizations that are elicited when pups are removed from their mothers. Disruption of a single copy of the gene led to modest developmental delay but a significant alteration in ultrasonic vocalization in response to such separation. Learning and memory appear normal in the heterozygous animals. Cerebellar abnormalities were observed in mice with disruptions in Foxp2, with Purkinje cells particularly affected. our findings support a role for Foxp2 in cerebellar development and in a developmental process that subsumes social communication functions in diverse organisms.