Clonal coat color variation due to a transforming gene expressed in melanocytes of transgenic mice.
Clonal coat color variation due to a transforming gene expressed in melanocytes of transgenic mice.
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由于转基因小鼠黑素细胞中表达的转化基因导致克隆毛色变化。
DOI：
10.1073/pnas.88.15.6447
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发表时间：
1991
影响因子：
11.1
通讯作者：
Mintz,B
中科院分区：
文献类型：
--
作者：
Bradl,M;Larue,L;Mintz,B
先前用Tyr-SV40E转基因产生近交黑色品系的转基因小鼠，该转基因包含由酪氨酸酶启动子驱动的猿病毒40转化序列，以获得黑色素瘤；人们发现这些动物的毛色比正常动物有不同程度的浅。如本文所述，色素沉着不足是由于体内毛球黑素细胞中黑化色素颗粒分化减少造成的，并且在培养的黑素细胞中自主发生。虽然一些小鼠有单色皮毛，但大多数（7/13）有两种或三种颜色的皮毛；此外，一位单色创始人产生了双色后代。这八只小鼠具有在自然基因型中看到的模式；最引人注目的是不同程度的横向条纹，背中线两侧有左右不对称的区域。这些图案显示了同种异体小鼠中显示的皮毛黑素细胞的相同克隆发育区域，这些小鼠是由不同颜色基因型的连体早期胚胎细胞形成的。一些 Tyr-SV40E 转基因也是细胞基因型嵌合体，可能是由于转基因的后期整合而产生的。然而，一只具有完全条纹皮毛的转基因创始人被证明是真正的繁殖者，具有常染色体遗传的图案。因此，遗传性条纹图案例证了同一类型细胞中表型不同但遗传相同的发育克隆或表型克隆的形成。该转基因小鼠品系为基因表达克隆变异的分子基础和同一个体中发生的黑素细胞致癌现象克隆的命运的实验分析提供了特殊的材料。
Transgenic mice of an inbred black strain were previously produced with the Tyr-SV40E transgene, comprising simian virus 40 transforming sequences driven by the tyrosinase promoter, in order to obtain melanomas; the animals were found to be lighter than normal in coat color, to various degrees. As described here, hypopigmentation resulted from diminished differentiation of melanized pigment granules in the melanocytes of the hair bulbs in vivo and occurred autonomously in cultured melanocytes. Whereas some of the mice had single-color coats, most (7/13) had coats of two or three colors; in addition, one single-color founder produced a two-color descendant. These eight mice had patterns seen in natural genotypes; the most striking were transversely striped to various extents, with regions of left-right asymmetry on either side of the dorsal midline. The patterns visualized the same clonal developmental territories of coat melanocytes displayed in allophenic mice that are formed from conjoined early embryo cells of different color genotypes. Some of the Tyr-SV40E transgenics were also cellular genotypic mosaics, probably arising by late integration of the transgene. However, one transgenic founder with a completely striped coat proved to be true-breeding, with autosomal inheritance of the pattern. The inherited striped pattern thus exemplifies the formation of phenotypically different but genetically identical developmental clones, or phenoclones, among cells of the same type. This line of transgenic mice provides exceptional material for experimental analysis of the molecular basis for clonal variation in gene expression and of the fate of oncogenic phenoclones of melanocytes occurring in the same individual.