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Cre recombinase‐dependent expression of a constitutively active mutant allele of the catalytic subunit of protein kinase A
Author(s) -
Niswender Colleen M.,
Willis Brandon S.,
Wallen Angela,
Sweet Ian R.,
Jetton Thomas L.,
Thompson Brian R.,
Wu Chaodong,
Lange Alex J.,
McKnight G. Stanley
Publication year - 2005
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/gene.20159
Subject(s) - glucokinase , biology , cre recombinase , protein kinase a , protein subunit , mutant , recombinase , microbiology and biotechnology , kinase , biochemistry , gene , transgene , recombination , genetically modified mouse
Using the cre‐loxP recombination system, we generated a line of mice expressing a constitutively active catalytic subunit of Protein Kinase A (PKA) in a temporally and spatially regulated fashion. In the absence of cre recombinase the modified catalytic subunit allele is functionally silent, but after recombination the mutant allele is expressed, resulting in enhanced PKA effects at basal cAMP levels. Mice expressing the modified protein in hepatocytes using albumin‐cre transgenics show defects in glucose homeostasis, glycogen storage, fructose 2,6‐bisphosphate levels, and induction of glucokinase mRNA during feeding. Similar to animals lacking glucokinase in the liver (Postic et al.: J Biol Chem 274:305–315, 1999), these mice also have defects in glucose‐stimulated insulin secretion, a hallmark of Type II diabetes. The widespread expression of PKA and the involvement of this kinase in a myriad of signaling pathways suggest that these animals will provide critical tools for the study of PKA function in vivo. genesis 43:109–119, 2005. © 2005 Wiley‐Liss, Inc.