Cre transgene results in global attenuation of the cAMP/PKA pathway.
Web of Science
AuthorGangoda, L; Doerflinger, M; Lee, YY; Rahimi, A; Etemadi, N; Chau, D; Milla, L; O'Connor, L; Puthalakath, H
Source TitleCell Death and Disease
PublisherSpringer Science and Business Media LLC
University of Melbourne Author/sDoerflinger, Marcel
AffiliationMedical Biology (W.E.H.I.)
Document TypeJournal Article
CitationsGangoda, L., Doerflinger, M., Lee, Y. Y., Rahimi, A., Etemadi, N., Chau, D., Milla, L., O'Connor, L. & Puthalakath, H. (2012). Cre transgene results in global attenuation of the cAMP/PKA pathway.. Cell Death Dis, 3 (8), pp.e365-. https://doi.org/10.1038/cddis.2012.110.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434654
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.
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