Feng L, Seymour A B, Jiang S, To A, Peden A A, Novak E K, Zhen L, Rusiniak M E, Eicher E M, Robinson M S, Gorin M B, Swank R T
Department of Molecular and Cell Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo NY 14263, USA.
Hum Mol Genet. 1999 Feb;8(2):323-30. doi: 10.1093/hmg/8.2.323.
Lysosomes, melanosomes and platelet-dense granules are abnormal in the mouse hypopigmentation mutant pearl. The beta3A subunit of the AP-3 adaptor complex, which likely regulates protein trafficking in the trans - Golgi network/endosomal compartments, was identified as a candidate for the pearl gene by a positional/candidate cloning approach. Mutations, including a large internal tandem duplication and a deletion, were identified in two respective pearl alleles and are predicted to abrogate function of the beta3A protein. Significantly lowered expression of altered beta3A transcripts occurred in kidney of both mutant alleles. The several distinct pearl phenotypes suggest novel functions for the AP-3 complex in mammals. These experiments also suggest mutations in AP-3 subunits as a basis for unique forms of human Hermansky-Pudlak syndrome and congenital night blindness, for which the pearl mouse is an appropriate animal model.
在小鼠色素减退突变体“珍珠”中，溶酶体、黑素小体和血小板致密颗粒均异常。AP-3衔接复合体的β3A亚基可能在反式高尔基体网络/内体区室中调节蛋白质运输，通过定位/候选克隆方法，该亚基被确定为“珍珠”基因的候选基因。在两个各自的“珍珠”等位基因中鉴定出了包括一个大的内部串联重复和一个缺失在内的突变，预计这些突变会消除β3A蛋白的功能。两个突变等位基因的肾脏中，改变后的β3A转录本的表达均显著降低。几种不同的“珍珠”表型表明AP-3复合体在哺乳动物中具有新功能。这些实验还表明，AP-3亚基的突变是人类赫尔曼斯基-普德拉克综合征和先天性夜盲症独特形式的基础，而“珍珠”小鼠是研究这两种病症的合适动物模型。
