Cell-Type Specific Expression of a Dominant Negative PKA Mutation in Mice
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.Citation
PLoS One. 2011 Apr 12; 6(4):e18772ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0018772
Scopus Count
Related articles
- Inhibition of protein kinase A in murine enteric neurons causes lethal intestinal pseudo-obstruction.
- Authors: Howe DG, Clarke CM, Yan H, Willis BS, Schneider DA, McKnight GS, Kapur RP
- Issue date: 2006 Feb 15
- Cre recombinase-dependent expression of a constitutively active mutant allele of the catalytic subunit of protein kinase A.
- Authors: Niswender CM, Willis BS, Wallen A, Sweet IR, Jetton TL, Thompson BR, Wu C, Lange AJ, McKnight GS
- Issue date: 2005 Nov
- Increased basal cAMP-dependent protein kinase activity inhibits the formation of mesoderm-derived structures in the developing mouse embryo.
- Authors: Amieux PS, Howe DG, Knickerbocker H, Lee DC, Su T, Laszlo GS, Idzerda RL, McKnight GS
- Issue date: 2002 Jul 26
- Chemoprevention with protein kinase A RIalpha antisense in DMBA-mammary carcinogenesis.
- Authors: Nesterova MV, Cho-Chung YS
- Issue date: 2005 Nov
- Regulation of the preprotachykinin-I gene promoter through a protein kinase A-dependent, cyclic AMP response element-binding protein-independent mechanism.
- Authors: Calin-Jageman IE, Wang J, Bannon MJ
- Issue date: 2006 Apr