Hdl Handle:
http://hdl.handle.net/10675.2/649
Title:
Cell-Type Specific Expression of a Dominant Negative PKA Mutation in Mice
Authors:
Willis, Brandon S.; Niswender, Colleen M.; Su, Thomas; Amieux, Paul S.; McKnight, G. Stanley
Abstract:
We employed the Cre recombinase/loxP system to create a mouse line in which PKA activity can be inhibited in any celltype that expresses Cre recombinase. The mouse line carries a mutant Prkar1a allele encoding a glycine to aspartate substitution at position 324 in the carboxy-terminal cAMP-binding domain (site B). This mutation produces a dominant negative RIa regulatory subunit (RIaB) and leads to inhibition of PKA activity. Insertion of a loxP-flanked neomycin cassette in the intron preceding the site B mutation prevents expression of the mutant RIaB allele until Cre-mediated excision of the cassette occurs. Embryonic stem cells expressing RIaB demonstrated a reduction in PKA activity and inhibition of cAMPresponsive gene expression. Mice expressing RIaB in hepatocytes exhibited reduced PKA activity, normal fasting induced gene expression, and enhanced glucose disposal. Activation of the RIaB allele in vivo provides a novel system for the analysis of PKA function in physiology.
Editors:
Mei, Lin
Citation:
PLoS One. 2011 Apr 12; 6(4):e18772
Issue Date:
12-Apr-2011
URI:
http://hdl.handle.net/10675.2/649
DOI:
10.1371/journal.pone.0018772
PubMed ID:
21533282
PubMed Central ID:
PMC3075275
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Neurology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorWillis, Brandon S.en_US
dc.contributor.authorNiswender, Colleen M.en_US
dc.contributor.authorSu, Thomasen_US
dc.contributor.authorAmieux, Paul S.en_US
dc.contributor.authorMcKnight, G. Stanleyen_US
dc.contributor.editorMei, Lin-
dc.date.accessioned2012-10-26T16:26:59Z-
dc.date.available2012-10-26T16:26:59Z-
dc.date.issued2011-04-12en_US
dc.identifier.citationPLoS One. 2011 Apr 12; 6(4):e18772en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid21533282en_US
dc.identifier.doi10.1371/journal.pone.0018772en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/649-
dc.description.abstractWe employed the Cre recombinase/loxP system to create a mouse line in which PKA activity can be inhibited in any celltype that expresses Cre recombinase. The mouse line carries a mutant Prkar1a allele encoding a glycine to aspartate substitution at position 324 in the carboxy-terminal cAMP-binding domain (site B). This mutation produces a dominant negative RIa regulatory subunit (RIaB) and leads to inhibition of PKA activity. Insertion of a loxP-flanked neomycin cassette in the intron preceding the site B mutation prevents expression of the mutant RIaB allele until Cre-mediated excision of the cassette occurs. Embryonic stem cells expressing RIaB demonstrated a reduction in PKA activity and inhibition of cAMPresponsive gene expression. Mice expressing RIaB in hepatocytes exhibited reduced PKA activity, normal fasting induced gene expression, and enhanced glucose disposal. Activation of the RIaB allele in vivo provides a novel system for the analysis of PKA function in physiology.en_US
dc.rightsWillis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectGeneticsen_US
dc.subjectGene Expressionen_US
dc.subjectGene Networksen_US
dc.subjectGenetic Mutationen_US
dc.subjectMolecular Geneticsen_US
dc.subjectModel Organismsen_US
dc.subjectAnimal Modelsen_US
dc.subjectMouseen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectGene Expressionen_US
dc.subjectSignal Transductionen_US
dc.titleCell-Type Specific Expression of a Dominant Negative PKA Mutation in Miceen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3075275en_US
dc.contributor.corporatenameDepartment of Neurology-

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