title: Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-Pudlak syndrome types 5 and 6.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Baohui
authors.initials: B
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Naoki
authors.initials: N
authors.lastname: Oiso
authors.forename: Edward K
authors.initials: EK
authors.lastname: Novak
authors.forename: Michael E
authors.initials: ME
authors.lastname: Rusiniak
authors.forename: Rashi
authors.initials: R
authors.lastname: Gautam
authors.forename: Sreenivasulu
authors.initials: S
authors.lastname: Chintala
authors.forename: Edward P
authors.initials: EP
authors.lastname: O'Brien
authors.forename: Yuke
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Roe
authors.forename: Rosemary W
authors.initials: RW
authors.lastname: Elliott
authors.forename: Eva M
authors.initials: EM
authors.lastname: Eicher
authors.forename: Ping
authors.initials: P
authors.lastname: Liang
authors.forename: Christian
authors.initials: C
authors.lastname: Kratz
authors.forename: Eric
authors.initials: E
authors.lastname: Legius
authors.forename: Richard A
authors.initials: RA
authors.lastname: Spritz
authors.forename: T Norene
authors.initials: TN
authors.lastname: O'Sullivan
authors.forename: Neal G
authors.initials: NG
authors.lastname: Copeland
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Jenkins
authors.forename: Richard T
authors.initials: RT
authors.lastname: Swank
mesh_terms: D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D027042:Chromosomes, Artificial, P1 Bacteriophage / Q000235:genetics; D004195:Disease Models, Animal; D029721:Drosophila Proteins; D005260:Female; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019476:Insect Proteins / Q000235:genetics*; D008297:Male; D020460:Melanosomes / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009842:Oligopeptides; D010455:Peptides / Q000276:immunology; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000276:immunology; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: C439973:AP3B1 protein, human; D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits; D033942:Adaptor Proteins, Vesicular Transport; D029721:Drosophila Proteins; C102160:HPS1 protein, human; C491131:Hps1 protein, mouse; D019476:Insect Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009842:Oligopeptides; D010455:Peptides; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; C410303:RB protein, Drosophila; C085706:FLAG peptide