title: Mouse pale ear (ep) is homologous to human Hermansky-Pudlak syndrome and contains a rare 'AT-AC' intron.
abstract: Hermansky-Pudlak syndrome (HPS) is a rare, often fatal, autosomal recessive disorder in which albinism, bleeding and lysosomal storage are associated with defects of diverse cytoplasmic organelles, including melanosomes, platelet dense granules and lysosomes. Similar multi-organellar defects occur in the Chediak-Higashi syndrome (CHS), as well as in a large number of different mouse mutants. The HPS gene is located in 10q23, and two genetically distinct mouse loci, pale ear (ep) and ruby-eye (ru), both with mutant phenotypes similar to human HPS, map close together in the homologous region of murine chromosome 19, suggesting that one of these loci might be homologous to human HPS. We recently identified the human HPS gene, which encodes a novel ubiquitously-expressed transmembrane protein of unknown function. Here, we describe characterization of the mouse Hps cDNA and genomic locus, and identification of pathologic Hps gene mutations in ep but not in ru mice, establishing mouse pale ear as an animal model for human HPS. The phenotype of homozygous ep mutant mice encompasses those of both HPS and CHS, suggesting that these disorders may be closely related. In addition, the mouse and human HPS genes both contain a rare 'AT-AC' intron, and comparison of the sequences of this intron in the mouse and human genes identified conserved sequences that suggest a possible role for pre-mRNA secondary structure in excision of this rare class of introns.
authors.affiliation: Department of Medical Genetics, University of Wisconsin, Madison 53706, USA.
authors.forename: G H
authors.initials: GH
authors.lastname: Feng
authors.forename: T
authors.initials: T
authors.lastname: Bailin
authors.forename: J
authors.initials: J
authors.lastname: Oh
authors.forename: R A
authors.initials: RA
authors.lastname: Spritz
mesh_terms: D016115:Albinism, Oculocutaneous / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004195:Disease Models, Animal; D004423:Ear / Q000473:pathology; D006720:Homozygote; D006801:Humans; D007438:Introns; D016464:Lysosomal Storage Diseases / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012322:RNA Precursors / Q000737:chemistry / Q000235:genetics; D012326:RNA Splicing; D012333:RNA, Messenger / Q000737:chemistry; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013577:Syndrome
chemical_list: C102160:HPS1 protein, human; C491131:Hps1 protein, mouse; D008565:Membrane Proteins; D012322:RNA Precursors; D012333:RNA, Messenger