Inducible expression of (V600E) Braf using tyrosinase-driven Cre recombinase results in embryonic lethality

Pigment Cell Melanoma Res. 2010 Feb;23(1):112-20. doi: 10.1111/j.1755-148X.2009.00662.x. Epub 2009 Dec 11.


We recently demonstrated that expression of (V600E)Braf in mature mouse melanocytes induces melanoma. Here, we show that expression of (V600E)Braf using the tyrosinase promoter leads to an unexpected embryonic lethality, with the animals dying before, at, or shortly after birth. The mice suffer from a range of developmental defects in the skin, the brain, the eyes and the heart, tissues that are normally colonized by melanocytes. We show that the (V600E)Braf expressing cells are potential melanocytic precursors that are fully transformed, suggesting that (V600E)Braf stimulates proliferation and blocks differentiation of these cells. Our data suggests that the presence of these cells in the organs that are normally occupied by melanocytes leads to severe developmental disruption, resulting in catastrophic defects and leading to death of the individual.

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Congenital Abnormalities / genetics*
  • Congenital Abnormalities / metabolism
  • Embryonic Development / genetics
  • Gene Expression Regulation, Developmental / genetics*
  • Gene Knock-In Techniques
  • Genes, Lethal / genetics*
  • Integrases / genetics
  • Melanocytes / metabolism
  • Melanoma / genetics
  • Melanoma / metabolism
  • Mice
  • Mice, Transgenic
  • Monophenol Monooxygenase / genetics
  • Promoter Regions, Genetic / genetics
  • Proto-Oncogene Proteins B-raf / genetics*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Stem Cells / metabolism


  • Monophenol Monooxygenase
  • Braf protein, mouse
  • Proto-Oncogene Proteins B-raf
  • Cre recombinase
  • Integrases