Inducible expression of V600EBraf using tyrosinase-driven Cre recombinase results in embryonic lethality

Abstract

Summary We recently demonstrated that expression of V600EBraf in mature mouse melanocytes induces melanoma. Here, we show that expression of V600EBraf 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 V600EBraf expressing cells are potential melanocytic precursors that are fully transformed, suggesting that V600EBraf 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. © 2009 John Wiley & Sons A/S.