The Protein Kinase KIS Impacts Gene Expression during Development and Fear Conditioning in Adult Mice

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The Protein Kinase KIS Impacts Gene Expression during Development and Fear Conditioning in Adult Mice

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dc.contributor.author Manceau, Valérie
dc.contributor.author Kremmer, Elisabeth
dc.contributor.author Maucuer, Alexandre
dc.contributor.author Nabel, Elizabeth G.
dc.date.accessioned 2013-03-29T18:21:14Z
dc.date.issued 2012
dc.identifier.citation Manceau, Valérie, Elisabeth Kremmer, Elizabeth G. Nabel, and Alexandre Maucuer. 2012. The protein kinase kis impacts gene expression during development and fear conditioning in adult mice. PLoS ONE 7(8): e43946. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:10475114
dc.description.abstract The brain-enriched protein kinase KIS (product of the gene UHMK1) has been shown to phosphorylate the human splicing factor SF1 in vitro. This phosphorylation in turn favors the formation of a \(U2AF^{65}\)-SF1-RNA complex which occurs at the 3′ end of introns at an early stage of spliceosome assembly. Here, we analyzed the effects of KIS knockout on mouse SF1 phosphorylation, physiology, adult behavior, and gene expression in the neonate brain. We found SF1 isoforms are differently expressed in KIS-ko mouse brains and fibroblasts. Re-expression of KIS in fibroblasts restores a wild type distribution of SF1 isoforms, confirming the link between KIS and SF1. Microarray analysis of transcripts in the neonate brain revealed a subtle down-regulation of brain specific genes including cys-loop ligand-gated ion channels and metabolic enzymes. Q-PCR analyses confirmed these defects and point to an increase of pre-mRNA over mRNA ratios, likely due to changes in splicing efficiency. While performing similarly in prepulse inhibition and most other behavioral tests, KIS-ko mice differ in spontaneous activity and contextual fear conditioning. This difference suggests that disregulation of gene expression due to KIS inactivation affects specific brain functions. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0043946 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427225/pdf/ en_US
dash.license LAA
dc.subject Biology en_US
dc.subject Biochemistry en_US
dc.subject Nucleic Acids en_US
dc.subject RNA en_US
dc.subject RNA processing en_US
dc.subject Genetics en_US
dc.subject Gene Splicing en_US
dc.subject Model Organisms en_US
dc.subject Animal Models en_US
dc.subject Molecular Cell Biology en_US
dc.subject Gene Expression en_US
dc.subject Neuroscience en_US
dc.subject Behavioral Neuroscience en_US
dc.subject Molecular Neuroscience en_US
dc.title The Protein Kinase KIS Impacts Gene Expression during Development and Fear Conditioning in Adult Mice en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Nabel, Elizabeth G.
dc.date.available 2013-03-29T18:21:14Z

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