Cable J, Barkway C, Steel K P
MRC Institute of Hearing Research, University Park, Nottingham, UK.
Hear Res. 1992 Dec;64(1):6-20. doi: 10.1016/0378-5955(92)90164-i.
The Wv mutation lies in the kinase domain of the proto-oncogene c-kit which is expressed in a variety of cells including neural crest derived melanoblasts. The mutation results in the abnormal migration, proliferation, survival and/or differentiation of melanoblasts. Viable Dominant Spotting (Wv/Wv) mouse mutants have a white coat due to the absence of melanocytes. The majority of these animals have no melanocytes within the stria vascularis and no endocochlear potential (EP). A proportion of homozygous mutants partially escape the effects of the mutation: 47.2% of pinnae and 21% of vestibular regions were pigmented and 10.8% of ears had an EP. All ears with an EP that were available for histology had some pigmentation of the stria. There was no obvious correlation between external and internal spotting in Wv/Wv mice, and asymmetrical pigmentation of the ears was common. Both light and dark intermediate cells (which are derived from melanocytes) were present in the middle and/or basal turns of these cochlear ducts and they appeared to function normally in enabling the stria to produce an EP (although the EP was usually lower than normal). This suggests that the c-kit gene product is needed only during development of the stria, and not for mature melanocyte function because the melanocytes present in the mutant strias were carrying the mutant version of the c-kit gene. Melanocytes were similar in appearance in controls and mutants, except that fewer melanin granules were observed in the strias of Wv/Wv mice. The observations that strial melanocytes with very few melanin granules in Wv/Wv mutants are able to support EP production, together with previous observations that albino animals with strial melanocytes but no melanin have a normal EP, suggest that melanocytes but not melanin are essential for normal strial function.
Wv突变位于原癌基因c-kit的激酶结构域，该基因在包括神经嵴衍生的黑素母细胞在内的多种细胞中表达。该突变导致黑素母细胞异常迁移、增殖、存活和/或分化。可行的显性斑点（Wv/Wv）小鼠突变体由于缺乏黑素细胞而具有白色被毛。这些动物中的大多数在血管纹内没有黑素细胞，也没有内耳蜗电位（EP）。一部分纯合突变体部分逃避了突变的影响：47.2%的耳廓和21%的前庭区域有色素沉着，10.8%的耳朵有EP。所有可用于组织学检查且有EP的耳朵，其血管纹都有一些色素沉着。Wv/Wv小鼠的外部和内部斑点之间没有明显的相关性，耳朵不对称色素沉着很常见。在这些耳蜗管的中阶和/或基底转中存在浅色和深色中间细胞（它们源自黑素细胞），并且它们似乎在使血管纹产生EP方面正常发挥作用（尽管EP通常低于正常水平）。这表明c-kit基因产物仅在血管纹发育期间需要，而对于成熟黑素细胞的功能则不需要，因为突变血管纹中存在的黑素细胞携带的是c-kit基因的突变版本。对照和突变体中的黑素细胞外观相似，只是在Wv/Wv小鼠的血管纹中观察到的黑素颗粒较少。Wv/Wv突变体中黑素颗粒极少的血管纹黑素细胞能够支持EP产生，以及先前观察到有血管纹黑素细胞但无黑色素的白化动物具有正常EP，这些观察结果表明黑素细胞而非黑色素对于正常的血管纹功能至关重要。
