Cable J, Huszar D, Jaenisch R, Steel K P
MRC Institute of Hearing Research, University Park, Nottingham, U.K.
Pigment Cell Res. 1994 Feb;7(1):17-32. doi: 10.1111/j.1600-0749.1994.tb00015.x.
The W locus encodes a tyrosine kinase receptor, c-kit, which affects survival of melanoblasts from the neural crest. The primary cochlear defect in Viable Dominant Spotting (Wv/Wv) mutants is a lack of melanocytes within the stria vascularis (SV) associated with an endocochlear potential (EP) close to zero and hearing impairment. In this study, we compare inner ear pigmentation with cochlear potentials in three other W alleles (Wx, Wsh, and W41) and reveal an unequivocal correlation between presence of strial melanocytes and presence of an EP. Asymmetry was common, and 8.3% of Wsh/Wx, 25% of Wsh/Wsh, 60% of W41/Wx, and 69.2% of W41/W41 ears had a pigmented stria and an EP, while the remainder had no strial melanocytes and no EP. In those mutants that partially escaped the effects of the mutation, strial melanocytes rarely extended the entire length of the stria, but were confined to the middle and/or basal turns of the cochlea. The extent of strial pigmentation was unrelated to the EP value, which was measured from the basal turn only. Compound action potential (CAP) responses recorded from ears with an EP were variable and they showed greatly raised thresholds or were absent in all ears where the EP was close to zero. In controls, melanocytes in the vestibular part of the ear were found in the utricle, crus commune, and ampullae, whereas in many mutants only one or two of these regions were pigmented. There was a broad correlation between pigmentation of the stria and pigmentation of the vestibular region but this was not absolute. All W41/Wx, Wsh/Wsh, and W41/W41 mutants had some pigment on the pinna but, in contrast to controls where melanocytes were found in the epidermis and dermis of the pinna, pigment cells were reduced in number and generally restricted to the dermis. Injection of normal neural crest cells into 9.5-day-old mutant embryos increased the extent of skin pigmentation on the head and coat of adult chimeras and was associated with a small increase in the proportion of pigmented strias.
W基因座编码一种酪氨酸激酶受体c-kit，它影响神经嵴黑素母细胞的存活。可行显性斑点（Wv/Wv）突变体的主要耳蜗缺陷是血管纹（SV）中缺乏黑素细胞，这与接近零的内耳蜗电位（EP）和听力障碍有关。在本研究中，我们比较了其他三个W等位基因（Wx、Wsh和W41）的内耳色素沉着与耳蜗电位，发现血管纹黑素细胞的存在与EP的存在之间存在明确的相关性。不对称情况很常见，8.3%的Wsh/Wx、25%的Wsh/Wsh、60%的W41/Wx和69.2%的W41/W41耳朵有色素沉着的血管纹和EP，而其余耳朵则没有血管纹黑素细胞和EP。在那些部分逃脱突变影响的突变体中，血管纹黑素细胞很少延伸到血管纹的全长，而是局限于耳蜗的中圈和/或基圈。血管纹色素沉着的程度与仅从基圈测量的EP值无关。从具有EP的耳朵记录的复合动作电位（CAP）反应各不相同，在所有EP接近零的耳朵中，它们显示出阈值大幅升高或没有反应。在对照组中，在内耳前庭部分的黑素细胞存在于椭圆囊、总脚和壶腹中，而在许多突变体中，这些区域中只有一两个有色素沉着。血管纹色素沉着与前庭区域色素沉着之间存在广泛的相关性，但并非绝对。所有W41/Wx、Wsh/Wsh和W41/W41突变体的耳廓上都有一些色素，但与对照组中黑素细胞存在于耳廓表皮和真皮不同，色素细胞数量减少，通常局限于真皮。将正常神经嵴细胞注射到9.5天大的突变胚胎中，增加了成年嵌合体头部和皮毛的皮肤色素沉着程度，并与有色素沉着的血管纹比例略有增加有关。
