| First Author | Willis BS | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 4 | Pages | e18772 |
| PubMed ID | 21533282 | Mgi Jnum | J:172384 |
| Mgi Id | MGI:5007582 | Doi | 10.1371/journal.pone.0018772 |
| Citation | Willis BS, et al. (2011) Cell-Type Specific Expression of a Dominant Negative PKA Mutation in Mice. PLoS One 6(4):e18772 |
| abstractText | We employed the Cre recombinase/loxP system to create a mouse line in which PKA activity can be inhibited in any cell-type 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 RIalpha regulatory subunit (RIalphaB) 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 RIalphaB allele until Cre-mediated excision of the cassette occurs. Embryonic stem cells expressing RIalphaB demonstrated a reduction in PKA activity and inhibition of cAMP-responsive gene expression. Mice expressing RIalphaB in hepatocytes exhibited reduced PKA activity, normal fasting induced gene expression, and enhanced glucose disposal. Activation of the RIalphaB allele in vivo provides a novel system for the analysis of PKA function in physiology. |
