title: Characterization of the murine gene corresponding to human Hermansky-Pudlak syndrome type 3: exclusion of the Subtle gray (sut) locus.
abstract: Hermansky-Pudlak syndrome (HPS) consists of oculocutaneous albinism and a bleeding diathesis due to absent platelet dense bodies. In addition to exhibiting considerable phenotypic variation, this autosomal recessive disorder displays locus heterogeneity. One causative gene is HPS1, coding for a protein of unknown function and resulting in HPS-1 disease, common in northwest Puerto Rico. A second HPS-causing gene is ADTB3A, coding for the beta3A subunit of adaptor complex-3 (AP-3, a coat protein complex) and resulting in HPS-2 disease. Each of these HPS subtypes has a murine counterpart, specifically pale ear for HPS-1 and pearl for HPS-2. Recently, the HPS3 gene, responsible for HPS-3 disease in a genetic isolate of central Puerto Rico, was isolated and characterized. Its location on human chromosome 3q24 suggested that the mouse model corresponding to HPS-3 disease might be subtle gray. To examine this possibility, we determined the mouse HPS3 sequence, its genomic organization, and its amino acid sequence, which shares 95.8% identity with the human protein. We demonstrated that the subtle gray mouse produces a normal size and amount of HPS3 mRNA and has an entirely normal sequence in every exon and intron/exon boundary. Furthermore, subtle gray exhibits a normal contingent of platelet dense bodies. Together, these data eliminate subtle gray as a murine model for HPS-3 disease and suggest that other mouse models be examined.
authors.affiliation: Section on Human Biochemical Genetics, Heritable Disorders Branch, Bethesda, Maryland 20892-1830, USA.
authors.forename: M
authors.initials: M
authors.lastname: Huizing
authors.forename: Y
authors.initials: Y
authors.lastname: Anikster
authors.forename: J G
authors.initials: JG
authors.lastname: White
authors.forename: W A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics*; D002648:Child; D004195:Disease Models, Animal; D005819:Genetic Markers / Q000235:genetics; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008875:Middle Aged; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid
chemical_list: D002352:Carrier Proteins; D005819:Genetic Markers; C432680:HPS3 protein, human; D047908:Intracellular Signaling Peptides and Proteins