mutation in archain 1, a subunit of copi coatomer complex, causes diluted coat color and purkinje cell degeneration突变archain 1亚基的copi coatomer复杂,导致稀释的外套颜色和浦肯野细胞变性.pdfVIP

Mutation in Archain 1, a Subunit of COPI Coatomer Complex, Causes Diluted Coat Color and Purkinje Cell Degeneration 1 2 1 1 3 Xinjie Xu , Rajendra Kedlaya , Hitoshi Higuchi , Sakae Ikeda , Monica J. Justice , Vijayasaradhi 2 1 Setaluri , Akihiro Ikeda * 1 Department of Medical Genetics, University of Wisconsin–Madison, Madison, Wisconsin, United States of America, 2 Department of Dermatology, University of Wisconsin–Madison, Madison, Wisconsin, United States of America, 3 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America Abstract Intracellular trafficking is critical for delivering molecules and organelles to their proper destinations to carry out normal cellular functions. Disruption of intracellular trafficking has been implicated in the pathogenesis of various neurodegenerative disorders. In addition, a number of genes involved in vesicle/organelle trafficking are also essential for pigmentation, and loss of those genes is often associated with mouse coat-color dilution and human hypopigmentary disorders. Hence, we postulated that screening for mouse mutants with both neurological defects and coat-color dilution will help identify additional factors associated with intracellular trafficking in neuronal cells. In this study, we characterized a mouse mutant with a unique N-ethyl-N-nitrosourea (ENU)–induced mutation, named nur17. nur17 mutant mice exhibit both coat-color dilution and ataxia due to Purkinje cell degeneration in the cerebellum. By positional cloning, we identified that the nur17 mouse carries a T-to-C missense mutation in archain 1 (Arcn1) gene which encodes the d subunit of the coat prot