Nguyen Thuyen, Novak Edward K, Kermani Maryam, Fluhr Joachim, Peters Luanne L, Swank Richard T, Wei Maria L
Department of Dermatology, Veterans Affairs Medical Center, University of California, San Francisco 94121, USA.
J Invest Dermatol. 2002 Nov;119(5):1156-64. doi: 10.1046/j.1523-1747.2002.19535.x.
Hermansky-Pudlak syndrome is an autosomal recessive disease characterized by pigment dilution and prolonged bleeding time. At least 15 mutant mouse strains have been classified as models of Hermansky-Pudlak syndrome. Some of the genes are implicated in intracellular vesicle trafficking: budding, targeting, and secretion. Many of the Hermansky-Pudlak syndrome genes remain uncharacterized and their functions are unknown. Clues to the functions of these genes can be found by analyzing the physiologic and cellular phenotypes. Here we have examined the morphology of the melanosomes in the skin of 10 of the mutant mouse Hermansky-Pudlak syndrome strains by transmission electron microscopy. We demonstrate that the morphologies reflect inhibition of organelle maturation or transfer. The Hermansky-Pudlak syndrome strains are classified into morphologic groups characterized by the step at which melanosome biogenesis or transfer to keratinocytes is inhibited, with the cappuccino strain observed to be blocked at the earliest step and gunmetal blocked at the latest step. We show that all Hermansky-Pudlak syndrome mutant strains except gunmetal have an increase in unpigmented or hypopigmented immature melanosomal forms, leading to the hypopigmented coat colors seen in these strains. In contrast, the hypopigmentation seen in the gunmetal strain is due to the retention of melanosomes in melanocytes, and inefficient transfer into keratinocytes.
Hermansky-Pudlak综合征是一种常染色体隐性疾病，其特征为色素稀释和出血时间延长。至少有15种突变小鼠品系已被归类为Hermansky-Pudlak综合征模型。其中一些基因与细胞内囊泡运输有关：出芽、靶向和分泌。许多Hermansky-Pudlak综合征相关基因仍未被鉴定，其功能也未知。通过分析生理和细胞表型可以找到这些基因功能的线索。在此，我们通过透射电子显微镜检查了10种突变型Hermansky-Pudlak综合征小鼠品系皮肤中黑素小体的形态。我们证明这些形态反映了细胞器成熟或转运的抑制。Hermansky-Pudlak综合征品系被分为不同的形态学组，其特征在于黑素小体生物合成或向角质形成细胞转运受到抑制的步骤，其中卡布奇诺品系在最早步骤被阻断，青铜色品系在最晚步骤被阻断。我们发现，除青铜色品系外，所有Hermansky-Pudlak综合征突变品系中无色素或色素减退的未成熟黑素小体形式均增加，导致这些品系出现毛色变浅。相比之下，青铜色品系中出现的色素减退是由于黑素小体保留在黑素细胞中，且向角质形成细胞的转运效率低下。
