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首页> 外文期刊>Molecular and Cellular Biology >Phenotypic reversions at the W/Kit locus mediated by mitotic recombination in mice.
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Phenotypic reversions at the W/Kit locus mediated by mitotic recombination in mice.

机译：W / Kit位点的表型逆转由小鼠的有丝分裂重组介导。

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The mouse W locus encodes Kit, the receptor tyrosine kinase for stem cell factor (SCF). Kit is required for several developmental processes, including the proliferation and survival of melanoblasts. Because of the nearly complete failure of Wrio/+ melanoblasts to colonize the skin, the costs of Wrio/+ mice are characterized by a majority of white hairs interspersed among pigmented hairs, giving a roan effect. However, 3.6% of Wrio/+ mice exhibit phenotypic reversions, i.e., spots of wild-type color on their coats with an otherwise mutant phenotype. Melanocyte cell lines were derived from each of six independent reversion spots on the skin of (C57BL/6 x DBA/2)F1 Wrio/+ mice. All six melanocyte cell lines exhibited the general characteristics common to normal, nonimmortal mouse melanocytes. Of these, three revertant cell lines had lost the dominant-negative Wrio allele following mitotic recombination between the centromere and the W locus. One of the cell lines remained Wrio/+ but showed (i) stimulation in response to SCF and (ii) increased Kit expression, suggesting that the Wrio mutation can be rescued by increased endogenous expression of the c-kit proto-oncogene. Finally, two cell lines showed no detectable genetic change at the W/Kit locus and failed to respond to SCF stimulation in vitro. These results demonstrate that mitotic recombination can create large patches of wild-type hair on the coats of Wrio/+ mutant mice. This shows that mitotic recombination occurs spontaneously in normal healthy tissue in vivo. Moreover, these experiments confirm that other mechanisms, not associated with loss of heterozygosity, may account for the coat color reversion phenotype.
机译：小鼠W基因座编码Kit，干细胞因子（SCF）的受体酪氨酸激酶。几个发育过程都需要试剂盒，包括黑素母细胞的增殖和存活。由于Wrio / +黑素母细胞几乎完全无法在皮肤上定植，因此Wrio / +小鼠的成本以大部分白发散布在有色毛发中为特征，从而产生了罗恩效应。但是，3.6％的Wrio / +小鼠表现出表型逆转，即在它们的被毛上带有其他突变表型的野生型色斑。黑色素细胞系来自（C57BL / 6 x DBA / 2）F1 Wrio / +小鼠皮肤上六个独立的逆转点。所有六个黑色素细胞系均表现出正常，非永生的小鼠黑色素细胞共有的一般特征。其中，三个着丝粒细胞系在着丝粒和W位点之间的有丝分裂重组后失去了显性阴性的Wrio等位基因。其中一种细胞系保持Wrio / +，但显示（i）响应SCF的刺激和（ii）Kit表达增加，这表明Wrio突变可通过c-kit原癌基因的内源性表达增加而得以挽救。最后，两种细胞系在W / Kit位点均未显示可检测的遗传变化，并且在体外对SCF刺激无反应。这些结果表明，有丝分裂重组可以在Wrio / +突变小鼠的皮毛上形成大块的野生型毛发。这表明在体内正常健康组织中自发发生有丝分裂重组。此外，这些实验证实，与杂合性丧失无关的其他机制可能是造成外套颜色回复表型的原因。

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