Reversible and tissue-specific activation of MAP kinase signaling by tamoxifen in brafV637ERT2 mice

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 BRAFV637EERT2 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 BrafV637EERT2 mice by a single injection of tamoxifen. BrafV637EERT2 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. genesis 51:448-455. (c) 2013 Wiley Periodicals, Inc.