G.W. Hooper Research Foundation, University of California San Francisco, 513 Parnassus Ave, San Francisco, CA 94143-0552, USA.
Transgenic Res. 2011 Apr;20(2):421-8. doi: 10.1007/s11248-010-9421-6. Epub 2010 Jun 25.
We have generated a novel transgenic mouse to direct inducible and reversible transgene expression in the melanocytic compartment. The Dopachrome tautomerase (Dct) control sequences we used are active early in the development of melanocytes and so this system was designed to enable the manipulation of transgene expression during development in utero and in the melanocyte stem cells as well as mature melanocytes. We observed inducible lacZ and GFP reporter transgene activity specifically in melanocytes and melanocyte stem cells in mouse skin. This mouse model will be a useful tool for the pigment cell community to investigate the contribution of candidate genes to normal melanocyte and/or melanoma development in vivo. Deregulated expression of the proto-oncogene MYC has been observed in melanoma, however whether MYC is involved in tumorigenesis in pigment cells has yet to be directly investigated in vivo. We have used our system to over-express MYC in the melanocytic compartment and show for the first time that increased MYC expression can indeed promote melanocytic tumor formation.
我们构建了一种新型的转基因小鼠，可在黑素细胞中实现诱导型和可逆的转基因表达。我们使用的多巴色素互变异构酶（Dct）调控序列在黑素细胞发育的早期就具有活性，因此该系统旨在实现在子宫内发育过程中以及黑素细胞干细胞和成熟黑素细胞中转基因表达的操纵。我们在小鼠皮肤中观察到诱导型 lacZ 和 GFP 报告基因转基因的活性特异性存在于黑素细胞和黑素细胞干细胞中。这种小鼠模型将成为色素细胞研究界的有用工具，可用于研究候选基因在体内对正常黑素细胞和/或黑色素瘤发育的贡献。原癌基因 MYC 的失调表达已在黑色素瘤中观察到，然而，MYC 是否参与了色素细胞的肿瘤发生尚未在体内进行直接研究。我们已经使用该系统在黑素细胞中过表达 MYC，并首次表明增加 MYC 的表达确实可以促进黑素细胞肿瘤的形成。
