title: Reversible and tissue-specific activation of MAP kinase signaling by tamoxifen in Braf(V637)ER(T2) mice.
abstract: Deregulated MAP kinase (MAPK) signaling plays key roles in developmental and adult disease processes, but the experimental activation of MAPK is a currently unresolved task. For the reversible induction of MAPK signaling, we generated transgenic mice harboring a tamoxifen inducible BRAF(V637E)ER(T2) fusion protein. The expression of the inducible BRAF kinase can be directed by Cre/loxP-mediated recombination to selected cell types and enables the highly specific activation of MAPK signalling in vivo. We show that MAPK signaling can be transiently activated in the brain, liver, or kidney of Braf(V637E)ER(T2) mice by a single injection of tamoxifen. Braf(V637E)ER(T2) mice provide a new versatile tool to study disease mechanisms elicited by MAPK activation, complementing gene knockout technology that is restricted to the analysis of loss-of-function phenotypes.
authors: Institute for Developmental Genetics, Helmholtz Zentrum München, 85764 Munich, Germany.
authors: Oskar
authors: O
authors: Ortiz
authors: Wolfgang
authors: W
authors: Wurst
authors: Ralf
authors: R
authors: Kühn
mesh_terms: D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D002478:Cells, Cultured; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic / Q000187:drug effects; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects*
chemical_list: D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D013629:Tamoxifen; C482120:Braf protein, mouse; D048493:Proto-Oncogene Proteins B-raf