Characterization of melanocyte-specific inducible Cre recombinase transgenic mice
Characterization of melanocyte-specific inducible Cre recombinase transgenic mice
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DOI：
10.1002/dvg.20205
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发表时间：
2006-05-01
期刊：
影响因子：
1.5
通讯作者：
Chin, L
中科院分区：
文献类型：
--
作者：
Bosenberg, M;Muthusamy, V;Chin, L
条件性Cre介导的重组已成为一种在小鼠中以器官特异性方式引入体细胞遗传改变的可靠方法。在此，我们构建并鉴定了在黑素细胞特异性酪氨酸酶启动子控制下携带4 - 羟基他莫昔芬（OHT）诱导型Cre重组酶 - 雌激素受体融合转基因的小鼠，将其命名为Tyr::CreER(T2)。在给予OHT后，Cre介导的重组以时空可控的方式在黑素细胞中被诱导，并在胚胎黑素母细胞、毛囊球黑素细胞、真皮树突状黑素细胞、尾部皮肤的表皮黑素细胞以及位于毛囊隆突内的假定黑素细胞干细胞中得到证实。表明毛囊黑素细胞干细胞中发生重组的功能性证据包括，在局部给予OHT 1年后，毛囊球黑素细胞中存在Cre介导的重组，此时已经历了几个毛发周期，位于该部位的黑素细胞已经历了多轮凋亡和补充。这些Tyr::CreER(T2)转基因小鼠为评估黑素细胞发育遗传学、表征黑素细胞干细胞功能和动力学以及构建精细的恶性黑色素瘤小鼠模型提供了有用的资源。
Conditional Cre-mediated recombination has emerged as a robust method of introducing somatic genetic alterations in an organ-specific manner in the mouse. Here, we generated and characterized mice harboring a 4-hydroxytamoxifen (OHT)-inducible Cre recombinase-estrogen receptor fusion transgene under the control of the melanocyte-specific tyrosinase promoter, designated Tyr::CreER(T2). Cre-mediated recombination was induced in melanocytes in a spatially and temporally controlled manner upon administration of OHT and was documented in embryonic melanoblasts, follicular bulb melanocytes, dermal dendritic melanocytes, epidermal melanocytes of tail skin, and in putative melanocyte stem cells located within the follicular bulge. Functional evidence suggestive of recombination in follicular melanocyte stem cells included the presence of Cre-mediated recombination in follicular bulb melanocytes 1 year after topical OHT administration, by which time several hair cycles have elapsed and the melanocytes residing in this location have undergone multiple rounds of apoptosis and replenishment. These Tyr::CreER(T2) transgenic mice represent a useful resource for the evaluation of melanocyte developmental genetics, the characterization of melanocyte stem cell function and dynamics, and the construction of refined mouse models of malignant melanoma.