幼鼠 Foxp2 敲出影响其发出正常超声 熊荣川 译 摘要： 言语和语言的神经生物学研究早先在 KE 家系中展开，该家系一半的成员患有严重的言语和语言障碍。和该表型相关的基因被定位到 7 号染色体上（ 7q31 ），鉴定为 FOXP2 基因，一种包含一个多谷氨酸通道和一个 DNA 叉头结合域的转录因子。因为连锁研究表明染色体区域 7q31 和自闭症有关联，该症状中语言障碍也是症状之一。而且，在具体的语言障碍研究中，认为 FOXP2 是一个潜在的与自闭症并发语言缺陷以及（或者）单纯语言障碍相关的基因位点。本文描述了鼠 Foxp2 基因缺陷小鼠的特征。双拷贝 Foxp2 缺陷基因导致严重的运动障碍、过早死亡以及在与母亲隔离时不能像正常小鼠一样发出超声。单拷贝的基因干扰导致中度发育延迟但对隔离时发出的超声影响明显。在杂合子动物模型中，学习和记忆都表现正常。在 Foxp2 干扰小鼠中还观察到了小脑畸形，尤其是对纤维细胞的影响最为突出。我们的研究结果支持 Foxp2 在小脑发育及与不同动物社交相关的发育过程中发挥有重要作用的观点。 关键词： 自闭症 小脑 交流 语言 言语 Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene 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 andor 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. 文献来源： Shu W. G., Cho J. Y., Jiang Y. H., Zhang M. H., Weisz D., Elder G. A., Schmeidler J., De Gasperi R., Sosa M. A. G., Rabidou D., Santucci A. C., Perl D., Morrisey E.,Buxbaum J. D. (2005). Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene. Proceedings of the National Academy of Sciences of the United States of America 102 (27): 9643-9648.
标签: 言语
