Zhang Qing, Zhao Baohui, Li Wei, Oiso Naoki, Novak Edward K, Rusiniak Michael E, Gautam Rashi, Chintala Sreenivasulu, O'Brien Edward P, Zhang Yuke, Roe Bruce A, Elliott Rosemary W, Eicher Eva M, Liang Ping, Kratz Christian, Legius Eric, Spritz Richard A, O'Sullivan T Norene, Copeland Neal G, Jenkins Nancy A, Swank Richard T
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Nat Genet. 2003 Feb;33(2):145-53. doi: 10.1038/ng1087. Epub 2003 Jan 27.
Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous disease involving abnormalities of melanosomes, platelet dense granules and lysosomes. Here we have used positional candidate and transgenic rescue approaches to identify the genes mutated in ruby-eye 2 and ruby-eye mice (ru2 and ru, respectively), two 'mimic' mouse models of HPS. We also show that these genes are orthologs of the genes mutated in individuals with HPS types 5 and 6, respectively, and that their protein products directly interact. Both genes are previously unknown and are found only in higher eukaryotes, and together represent a new class of genes that have evolved in higher organisms to govern the synthesis of highly specialized lysosome-related organelles.
赫尔曼斯基-普德拉克综合征（HPS）是一种基因异质性疾病，涉及黑素小体、血小板致密颗粒和溶酶体的异常。在此，我们采用定位候选基因和转基因拯救方法，来鉴定红宝石眼2型和红宝石眼小鼠（分别为ru2和ru）中发生突变的基因，这两种小鼠是HPS的“模拟”模型。我们还表明，这些基因分别是5型和6型HPS患者中发生突变的基因的直系同源基因，并且它们的蛋白质产物直接相互作用。这两个基因以前均不为人知，且仅在高等真核生物中发现，它们共同代表了一类在高等生物中进化而来的新基因，用于调控高度特化的溶酶体相关细胞器的合成。
