title: Cre transgene results in global attenuation of the cAMP/PKA pathway.
abstract: Use of the cre transgene in in vivo mouse models to delete a specific 'floxed' allele is a well-accepted method for studying the effects of spatially or temporarily regulated genes. During the course of our investigation into the effect of cyclic adenosine 3',5'-monophosphate-dependent protein kinase A (PKA) expression on cell death, we found that cre expression either in cultured cell lines or in transgenic mice results in global changes in PKA target phosphorylation. This consequently alters gene expression profile and changes in cytokine secretion such as IL-6. These effects are dependent on its recombinase activity and can be attributed to the upregulation of specific inhibitors of PKA (PKI). These results may explain the cytotoxicity often associated with cre expression in many transgenic animals and may also explain many of the phenotypes observed in the context of Cre-mediated gene deletion. Our results may therefore influence the interpretation of data generated using the conventional cre transgenic system.
authors.affiliation: Department of Biochemistry, La Trobe Institute of Molecular Science, La Trobe University, Kingsbury Drive, Bundoora, Victoria, Australia 3086.
authors.forename: L
authors.initials: L
authors.lastname: Gangoda
authors.forename: M
authors.initials: M
authors.lastname: Doerflinger
authors.forename: Y Y
authors.initials: YY
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Rahimi
authors.forename: N
authors.initials: N
authors.lastname: Etemadi
authors.forename: D
authors.initials: D
authors.lastname: Chau
authors.forename: L
authors.initials: L
authors.lastname: Milla
authors.forename: L
authors.initials: L
authors.lastname: O'Connor
authors.forename: H
authors.initials: H
authors.lastname: Puthalakath
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015536:Down-Regulation; D017353:Gene Deletion; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D015398:Signal Transduction; D019076:Transgenes; D015854:Up-Regulation
chemical_list: D015850:Interleukin-6; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C045073:Cre recombinase; D019426:Integrases