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Inducible expression of V600E Braf using tyrosinase‐driven Cre recombinase results in embryonic lethality
Author(s) -
Dhomen Nathalie,
Da Rocha Dias Silvy,
Hayward Robert,
Ogilvie Lesley,
Hedley Douglas,
Delmas Veronique,
McCarthy Afshan,
Henderson Deborah,
Springer Caroline J.,
Pritchard Catrin,
Larue Lionel,
Marais Richard
Publication year - 2010
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2009.00662.x
Subject(s) - lethality , recombinase , embryonic stem cell , synthetic lethality , cre recombinase , biology , cancer research , microbiology and biotechnology , genetics , gene , recombination , dna repair , transgene , genetically modified mouse
Summary 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.