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Cell Rep. 2014 Sep 11;8(5):1257-64. doi: 10.1016/j.celrep.2014.07.047. Epub 2014 Aug 21.

RacGAP α2-chimaerin function in development adjusts cognitive ability in adulthood.

Author information

1
Division of Neurogenetics, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan; Department of Genetics, The Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka 411-8540, Japan.
2
Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
3
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
4
Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Department of Molecular Neuropsychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
5
Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Suita, Osaka 565-0871, Japan.
6
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan. Electronic address: sitohara@brain.riken.jp.
7
Division of Neurogenetics, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan; Department of Genetics, The Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka 411-8540, Japan. Electronic address: tiwasato@nig.ac.jp.

Abstract

A major concern in neuroscience is how cognitive ability in adulthood is affected and regulated by developmental mechanisms. The molecular bases of cognitive development are not well understood. We provide evidence for the involvement of the α2 isoform of Rac-specific guanosine triphosphatase (GTPase)-activating protein (RacGAP) α-chimaerin (chimerin) in this process. We generated and analyzed mice with global and conditional knockouts of α-chimaerin and its isoforms (α1-chimaerin and α2-chimaerin) and found that α-chimaerin plays a wide variety of roles in brain function and that the roles of α1-chimaerin and α2-chimaerin are distinct. Deletion of α2-chimaerin, but not α1-chimaerin, beginning during early development results in an increase in contextual fear learning in adult mice, whereas learning is not altered when α2-chimaerin is deleted only in adulthood. Our findings suggest that α2-chimaerin acts during development to establish normal cognitive ability in adulthood.

PMID:
25159148
DOI:
10.1016/j.celrep.2014.07.047
[Indexed for MEDLINE]
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