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dc.contributor.authorManceau, Valérie
dc.contributor.authorKremmer, Elisabeth
dc.contributor.authorNabel, Elizabeth G.
dc.contributor.authorMaucuer, Alexandre
dc.date.accessioned2013-03-29T18:21:14Z
dc.date.issued2012
dc.identifier.citationManceau, 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.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10475114
dc.description.abstractThe 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.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0043946en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427225/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectBiochemistryen_US
dc.subjectNucleic Acidsen_US
dc.subjectRNAen_US
dc.subjectRNA processingen_US
dc.subjectGeneticsen_US
dc.subjectGene Splicingen_US
dc.subjectModel Organismsen_US
dc.subjectAnimal Modelsen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectGene Expressionen_US
dc.subjectNeuroscienceen_US
dc.subjectBehavioral Neuroscienceen_US
dc.subjectMolecular Neuroscienceen_US
dc.titleThe Protein Kinase KIS Impacts Gene Expression during Development and Fear Conditioning in Adult Miceen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorNabel, Elizabeth G.
dc.date.available2013-03-29T18:21:14Z
dc.identifier.doi10.1371/journal.pone.0043946*
dash.contributor.affiliatedNabel, Elizabeth


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