Melanosome morphologies in murine models of Hermansky-Pudlak syndrome reflect blocks in organelle development
Melanosome morphologies in murine models of Hermansky-Pudlak syndrome reflect blocks in organelle development
复制标题
DOI：
10.1046/j.1523-1747.2002.19535.x
复制
发表时间：
2002-11-01
影响因子：
6.5
通讯作者：
Wei, ML
中科院分区：
文献类型：
--
作者：
Nguyen, T;Novak, EK;Wei, ML
Hermansky-Pudlak综合征是一种常染色体隐性遗传病，以色素稀释和出血时间延长为特征。至少有15个突变小鼠品系被归类为Hermansky-Pudlak综合征的模型。其中一些基因与细胞内的囊泡运输有关：萌芽、靶向和分泌。许多Hermansky-Pudlak综合征的基因仍然没有特征，它们的功能也不清楚。通过分析这些基因的生理和细胞表型，可以找到这些基因功能的线索。在这里，我们用透射电子显微镜观察了10只突变的Hermansky-Pudlak综合征小鼠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移的抑制。Hermansky-Pudlak综合征菌株被分成以黑素小体生物生成或向角质形成细胞转移被抑制的步骤为特征的形态组，观察到卡布奇诺菌株在最早的步骤被阻止，而枪金属菌株在最晚的步骤被阻止。我们发现，除枪金属外，所有Hermansky-Pudlak综合征突变株的未成熟黑素体无色素或色素降低的形式都增加，导致这些菌株出现色素降低的毛色。相比之下，在枪金属菌株中看到的色素减退是由于黑素细胞中黑素小体的保留，以及向角质形成细胞的低效转移。
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.