期刊
NEUROSCIENCE LETTERS
卷 506, 期 2, 页码 277-280出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2011.11.022
关键词
Foxp2; CtBP; Speech-language; Cntnap2
资金
- Ministry of Education, Culture, Sports, Science and Technology, Japan [21200011, 21700377]
- Ministry of the Health, Labour and Welfare, Japan [10103243]
- Grants-in-Aid for Scientific Research [21700377, 21200011] Funding Source: KAKEN
Foxp2(R552H) knock-in (KI) mice carrying a mutation related to human speech-language disorder exhibit impaired ultrasonic vocalization and poor Purkinje cell development. Foxp2 is a forkhead domain-containing transcriptional repressor that associates with its co-repressor CtBP; Foxp2(R552H) displays reduced DNA binding activity. A genetic connection between FOXP2 and CNTNAP2 has been demonstrated in vitro, but not in vivo. Here we show that Cntnap2 mRNA levels significantly increased in the cerebellum of Foxp2(R552H) KI pups, although the cerebellar population of Foxp2-positive Purkinje cells was very small. Furthermore, Cntnap2 immunofluorescence did not decrease in the poorly developed Purkinje cells of Foxp2(R552H) KI pups, although synaptophysin immunofluorescence decreased. Cntnap2 and CtBP were ubiquitously expressed, while Foxp2 co-localized with CtBP only in Purkinje cells. Taken together, these observations suggest that Foxp2 may regulate ultrasonic vocalization by associating with CtBP in Purkinje cells; Cntnap2 may be a target of this co-repressor. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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