2011 Fiscal Year Final Research Report
The mechanisms of language acquisition and evolution of mouse brain in Foxp2-KI mice
| Project/Area Number |
21200011
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neuroscience in general
Physical anthropology
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| Research Institution | International University of Health and Welfare |
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Principal Investigator |
MOMOI Takashi 国際医療福祉大学, 保健医療学部, 教授 (40143507)
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| Co-Investigator(Kenkyū-buntansha) |
MOMOI Mariko 自治医科大学, 医学部, 教授 (90166348)
JINBO Eriko 自治医科大学, 医学部, 講師 (20291651)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 進化 / 言語 / 言語障害 / Broca / FOXP2 |
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| Research Abstract |
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.
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