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

言语障碍的表型分离为常染色体显性性状。有一半的KE家族成员有严重的发音困难，伴有言语和口面功能障碍。错义突变（R553H）在FOXP2的叉头域与KE家族的受影响的成员共分离。我们使用Foxp2（R552 H）突变敲入小鼠，Foxp2（R552 H）-KI小鼠（Foxp2-KI小鼠）（与FOXP2（R553 H）突变相关），弥合了fMRI数据与言语语言能力之间的差距（PNAS 2008）。Foxp2-KI小鼠表现出受损的USV通讯。Foxp2（R552H）增加小脑CNTNAP 2基因表达（Neurosci. lett. 2012年）。FOXP2促进POT1的核转位，但FOXP2（R553H），一种与语言障碍相关的突变，部分阻止了它。浦肯野细胞树突上表达Cadm1的突触参与小鼠超声发声活动（PLoS One. 2012年）。我们通过使用Pcp2基因的BAC转基因和Foxp2（R552H）-KI/Pcp2-FOXP2-myc-Tg小鼠（Foxp2-KI/FOXP2-Tg）通过与Foxp2-KI小鼠交配产生了在浦肯野细胞中特异性表达人FOXP2的转基因小鼠系（Pcp2-FOXP2-myc-Tg; FOXP2-Tg），并检查了FOXP2对USV功能和浦肯野细胞的影响。

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.