Provance D W, Wei M, Ipe V, Mercer J A
McLaughlin Research Institute, Great Falls, MT 59405, USA.
Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14554-8. doi: 10.1073/pnas.93.25.14554.
Mutant alleles at the dilute unconventional myosin heavy chain locus cause diluted coat color, opisthotonic seizures, and death. The dilute coat color phenotype is caused by irregular clumping of pigment in the hair, but amounts of melanin are unchanged from wild-type controls. The melanocyte phenotype has been described as adendritic, since hair bulb and Harderian gland melanocytes appear to be rounded in tissue sections. These observations do not exclude the possibility that the processes lack pigment, since the melanocyte shape was judged by the distribution of melanin. We have tested this hypothesis by culturing primary melanocytes from dilute mutant and wild-type mice. The mutant melanocytes do not lack processes; instead, they exhibit a concentrated perinuclear distribution of melanosomes, while wild-type melanocytes have a very uniform cytoplasmic distribution of melanosomes. Electron micrographs show no detectable differences in melanosome morphology or maturation between dilute and wild-type melanocytes. Immunofluorescence experiments indicate that the dilute protein is concentrated in regions of the cytoplasm that contain melanosomes. These experiments show that the dilute myosin is necessary for the localization of melanosomes, either by active transport or tethering.
稀化非常规肌球蛋白重链基因座上的突变等位基因会导致毛色变浅、角弓反张性癫痫发作和死亡。毛色变浅的表型是由毛发中色素的不规则聚集引起的,但黑色素的含量与野生型对照相比没有变化。黑素细胞的表型被描述为无树突状,因为在组织切片中毛球和哈德氏腺黑素细胞似乎是圆形的。这些观察结果并不排除这些突起缺乏色素的可能性,因为黑素细胞的形状是通过黑色素的分布来判断的。我们通过培养来自稀化突变小鼠和野生型小鼠的原代黑素细胞来检验这一假设。突变型黑素细胞并不缺乏突起;相反,它们的黑素体呈现核周集中分布,而野生型黑素细胞的黑素体在细胞质中分布非常均匀。电子显微镜照片显示,稀化型和野生型黑素细胞在黑素体形态或成熟方面没有可检测到的差异。免疫荧光实验表明,稀化蛋白集中在含有黑素体的细胞质区域。这些实验表明,稀化肌球蛋白对于黑素体的定位是必需的,无论是通过主动运输还是拴系作用。