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

Foxp2-KI小鼠大脑语言习得和进化机制

基本信息

批准号：
21200011
负责人：
MOMOI Takashi
金额：
$ 18.72万
依托单位：
International University of Health and Welfare
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21200011/
关键词：
進化言語言語障害 Broca FOXP2

项目摘要

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.

语音障碍的表型将其视为常染色体显性特征。一半的KE家族患有语言障碍的成员遇到了严重的表达困难，并伴有言语和口头障碍。 FOXP2的叉子域中的错义突变（R553H）与受影响的家族的成员共隔离。我们使用FOXP2（R552H）突变，FOXP2（R552H）-KI小鼠（FOXP2-KI小鼠）（FOXP2（R5553H）突变（PNAS 2008），使用FOXP2（R552H）突变，FOXP2（R552H）突变，与FOXP2（R552H）突变，FOXP2（R552H）突变之间的敲击小鼠之间的差距弥合了差距。 FOXP2-KI小鼠表现出受损的USV通信。FOXP2（R552H）增加小脑CNTNAP2基因表达（Neurosci。Lett。2012）。 FOXP2促进了POT1的核易位，但是与语音语言障碍有关的FOXP2（R553H）突变部分阻止了IT。对Purkinje细胞树突上表达cadm1的突触参与小鼠超声声音活性（PlosOne。2012）。我们通过使用PCP2基因和FOXP2（R552H）-KI/ PCP2-FOXP2-FOXP2-FOXP2-MYC-TG小鼠（FOXP2-KI/ FOXP2-TG）的鼠标（FOXP2-ki/ foxp2-tg），通过使用PCP2基因和FoxP2-Foxp2-Foxp2-Foxp2-foxp2-tg的鼠标，通过使用PCP2基因和FOXP2-FOXP2-FOXP2-FOXP2-2-KKI的鼠标来生成在Purkinje细胞中特异性表达人FOXP2的转基因小鼠系（PCP2-FOXP2-MYC-TG; FOXP2-TG）。 USV函数和Purkinje细胞上的FOXP2。