Inducible expression of V600EBraf using tyrosinase-driven Cre recombinase results in embryonic lethality
Inducible expression of V600EBraf using tyrosinase-driven Cre recombinase results in embryonic lethality
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DOI：
10.1111/j.1755-148x.2009.00662.x
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发表时间：
2010-02-01
影响因子：
4.3
通讯作者：
Marais, Richard
中科院分区：
文献类型：
--
作者：
Dhomen, Nathalie;Dias, Silvy Da Rocha;Marais, Richard
我们最近证明，（V600 E）Braf在成熟小鼠黑素细胞中的表达诱导黑色素瘤。在这里，我们表明，表达（V600E）Braf使用酪氨酸酶启动子导致一个意想不到的胚胎致死率，与动物死亡之前，出生时，或出生后不久。这些小鼠在皮肤、大脑、眼睛和心脏等通常由黑素细胞定植的组织中存在一系列发育缺陷。我们表明，（V600E）Braf表达细胞是潜在的黑素细胞的前体，是完全转化，这表明（V600E）Braf刺激增殖和阻断这些细胞的分化。我们的数据表明，这些细胞在通常被黑色素细胞占据的器官中的存在会导致严重的发育中断，导致灾难性的缺陷并导致个体死亡。
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.