Reversible and tissue-specific activation of MAP kinase signaling by tamoxifen in Braf(V637)ER(T2) mice

Genesis. 2013 Jun;51(6):448-55. doi: 10.1002/dvg.22386. Epub 2013 Mar 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / growth & development
  • Brain / metabolism
  • Cells, Cultured
  • Kidney / metabolism
  • Liver / metabolism
  • MAP Kinase Signaling System*
  • Mice
  • Mice, Transgenic
  • Organ Specificity
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins B-raf / metabolism
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • Recombination, Genetic / drug effects
  • Spinal Cord / embryology
  • Spinal Cord / metabolism
  • Tamoxifen / pharmacology*
  • Transcriptional Activation / drug effects*

Substances

  • Receptors, Estrogen
  • Recombinant Fusion Proteins
  • Tamoxifen
  • Braf protein, mouse
  • Proto-Oncogene Proteins B-raf