The mechanisms of language acquisition and evolution of mouse brain in Foxp2-KI mice

言语-语言障碍的表型分离为常染色体显性性状。在患有言语-语言障碍的柯氏家族中，有一半的成员有严重的发音困难，并伴有语言和口腔功能障碍。FOXP2叉头区的一个错义突变(R553H)与KE家族中受影响的成员共分离。我们利用带有Foxp2(R552H)突变的敲入小鼠(Foxp2(R552H)-Ki小鼠)(Foxp2-Ki小鼠)，弥合了fMRI数据和语音语言能力之间的差距，Foxp2(R553H)突变与FOXP2(R553H)突变相关(PNAS 2008)。Foxp2-Ki小鼠表现出USV通讯障碍。Foxp2(R552H)增加小脑CNTNAP2基因的表达(Neurosci)。让我们来吧。2012年)。FOXP2促进POT1的核转位，而与言语语言障碍相关的突变FOXP2(R553H)部分阻止了POT1的核转位。浦肯野细胞树突上表达CAdm1的突触参与了小鼠超声发声活动(PLoS One)。2012年)。我们利用BAC转基因Pcp2基因和Foxp2(R552H)-Ki/Pcp2-FOXP2-myc-TG小鼠(Foxp2-Ki/FOXP2-TG)，建立了在Purkinje细胞中特异性表达人FOXP2的转基因小鼠系(Pcp2-FOXP2-myc-TG；FOXP2-TG)，并检测了FOXP2对USV功能和Purkinje细胞的影响。

The phenotype of speech-language disorder segregates as an autosomal dominant trait. One-half the members of the KE family with speech-language disorder have severe articulation difficulties accompanied by verbal and orofacial impairment. A missense mutation (R553H) in the forkhead domain of FOXP2 co-segregates with the affected members of the KE family. We have bridged the gap between the fMRI data and speech-language ability using knock-in mice with the Foxp2(R552H) mutation, Foxp2(R552H)-KI mice (Foxp2-KI mice), which is related to the FOXP2(R553H) mutation (PNAS 2008). Foxp2-KI mice exhibit impaired USV communication.Foxp2(R552H) increase cerebellar CNTNAP2 gene expression (Neurosci. Lett. 2012). FOXP2 promotes the nuclear translocation of POT1, but FOXP2(R553H), mutation related to speech-language disorder, partially prevents it.Cadm1-expressing synapses on Purkinje cell dendrites are involved in mouse ultrasonic vocalization activity (PLoS One. 2012). We generated transgenic mouse lines (Pcp2-FOXP2-myc-Tg;FOXP2-Tg) that specifically express human FOXP2 in Purkinje cells, by using BAC transgenesis of Pcp2 gene and Foxp2(R552H)-KI/ Pcp2-FOXP2-myc-Tg mice (Foxp2-KI/FOXP2-Tg) by mating with Foxp2-KI mice and examined the effects of FOXP2 on the USV function and Purkinje cells.