title: The mouse pale ear (ep) mutation is the homologue of human Hermansky-Pudlak syndrome.
abstract: The recessive mutation at the pale ear (ep) locus on mouse chromosome 19 was found to be the homologue of human Hermansky-Pudlak syndrome (HPS). A positional cloning strategy using yeast artificial chromosomes spanning the HPS locus was used to identify the HPS gene and its murine counterpart. These genes and their predicted proteins are highly conserved at the nucleotide and amino acid levels. Sequence analysis of the mutant ep gene revealed the insertion of an intracisternal A particle element in a protein-coding 3' exon. Here we demonstrate that mice with the ep mutation exhibit abnormalities similar to human HPS patients in melanosomes and platelet-dense granules. These results establish an animal model of HPS and will facilitate biochemical and molecular analyses of the functions of this protein in the membranes of specialized intracellular organelles.
authors.affiliation: The Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Gardner
authors.forename: S C
authors.initials: SC
authors.lastname: Wildenberg
authors.forename: N M
authors.initials: NM
authors.lastname: Keiper
authors.forename: E K
authors.initials: EK
authors.lastname: Novak
authors.forename: M E
authors.initials: ME
authors.lastname: Rusiniak
authors.forename: R T
authors.initials: RT
authors.lastname: Swank
authors.forename: N
authors.initials: N
authors.lastname: Puri
authors.forename: J N
authors.initials: JN
authors.lastname: Finger
authors.forename: N
authors.initials: N
authors.lastname: Hagiwara
authors.forename: A L
authors.initials: AL
authors.lastname: Lehman
authors.forename: T L
authors.initials: TL
authors.lastname: Gales
authors.forename: M E
authors.initials: ME
authors.lastname: Bayer
authors.forename: R A
authors.initials: RA
authors.lastname: King
authors.forename: M H
authors.initials: MH
authors.lastname: Brilliant
mesh_terms: D016115:Albinism, Oculocutaneous / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid