Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-Pudlak syndrome types 5 and 6

Nat Genet. 2003 Feb;33(2):145-53. doi: 10.1038/ng1087. Epub 2003 Jan 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Protein Complex 3
  • Adaptor Protein Complex beta Subunits
  • Adaptor Proteins, Vesicular Transport*
  • Adult
  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Child, Preschool
  • Chlorocebus aethiops
  • Chromosomes, Artificial, Bacterial / genetics
  • Chromosomes, Artificial, P1 Bacteriophage / genetics
  • Disease Models, Animal
  • Drosophila Proteins*
  • Female
  • Hermanski-Pudlak Syndrome / genetics*
  • Hermanski-Pudlak Syndrome / metabolism
  • Hermanski-Pudlak Syndrome / pathology
  • Humans
  • Insect Proteins / genetics*
  • Male
  • Melanosomes / genetics
  • Membrane Proteins / genetics*
  • Membrane Transport Proteins*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mutation / genetics*
  • Oligopeptides
  • Peptides / immunology
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Proteins / genetics*
  • Proto-Oncogene Proteins c-myc / immunology
  • Saccharomyces cerevisiae / metabolism
  • Sequence Homology, Amino Acid
  • Transfection
  • Two-Hybrid System Techniques

Substances

  • AP3B1 protein, human
  • Adaptor Protein Complex 3
  • Adaptor Protein Complex beta Subunits
  • Adaptor Proteins, Vesicular Transport
  • Drosophila Proteins
  • HPS1 protein, human
  • Hps1 protein, mouse
  • Insect Proteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • Oligopeptides
  • Peptides
  • Proteins
  • Proto-Oncogene Proteins c-myc
  • RB protein, Drosophila
  • FLAG peptide

Associated data

  • GENBANK/AF534396
  • GENBANK/AF534397
  • GENBANK/AF534398
  • GENBANK/AF534399
  • GENBANK/AF534400
  • GENBANK/AF534401
  • GENBANK/AF534402
  • GENBANK/AF536238
  • GENBANK/AF536239