Hermansky-Pudlak HPS1/pale ear gene regulates epidermal and dermal melanocyte development
Hermansky-Pudlak HPS1/pale ear gene regulates epidermal and dermal melanocyte development
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DOI：
10.1038/sj.jid.5700566
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发表时间：
2007-02-01
影响因子：
6.5
通讯作者：
Wei, Maria L.
中科院分区：
文献类型：
--
作者：
Nguyen, Thuyen;Wei, Maria L.
白耳（ep）小鼠品系是Hermansky-Pudlak综合征1型（HPS-1）的模型，HPS-1是一种常染色体隐性遗传疾病，可引起色素稀释、视觉障碍、出血素质、肺纤维化和肉芽肿性结肠炎。ep小鼠的毛色与黑色亲本品系C57 BL/6非常相似。然而，与对照组相比，ep小鼠的耳朵和尾巴明显色素减退，这表明ep小鼠的基因突变揭示了背部皮肤黑素细胞与尾巴或耳朵皮肤黑素细胞功能的差异调节。在这项研究中，我们详细分析了突变表型，并确定在尾部，缺陷基因导致延迟发病的滤泡间表皮黑素细胞酪氨酸酶活性，滤泡间表皮和真皮中的黑素细胞数量减少，以及尾部表皮黑素体严重不成熟，在背侧滤泡黑素细胞中未观察到的发现。这些结果突出了滤泡和滤泡间黑素细胞生物学的差异，并证明ep蛋白的缺陷不仅影响黑素体的生物发生，而且在决定滤泡间表皮和真皮黑素细胞功能方面发挥了发育作用。这些研究结果的机制，在人类色素沉着的生理变化和白癜风的发病机制进行了讨论。
The pale ear (ep) mouse strain is a model for the Hermansky-Pudlak syndrome type 1 (HPS-1), an autosomal recessive disorder causing pigmentary dilution, visual disturbances, bleeding diatheses, pulmonary fibrosis, and granulomatous colitis. The ep mice have a coat color very similar to the black-colored parental strain, C57BL/6. However, the ears and tails of ep mice are significantly hypopigmented compared with the control animals, suggesting that the gene mutation in ep mice reveals a differential regulation of melanocyte function in dorsal back skin melanocytes versus tail or ear skin. In this study, we analyzed the mutant phenotype in detail and determined that in the tail, the defective gene causes delayed onset of interfollicular epidermal melanocyte tyrosinase activity, decreased numbers of melanocytes in the interfollicular epidermis and dermis, and severe immaturity of tail epidermal melanosomes, findings not observed in dorsal back follicular melanocytes. These results highlight differences between follicular and interfollicular melanocyte biology and demonstrate that defects in the ep protein not only affect melanosome biogenesis, but also play a developmental role in determining interfollicular epidermal and dermal melanocyte function. The implications of these findings for the mechanisms governing physiologic variation in human pigmentation and for the pathogenesis of vitiligo are discussed.