title: The mouse organellar biogenesis mutant buff results from a mutation in Vps33a, a homologue of yeast vps33 and Drosophila carnation.
abstract: In the mouse, more than 16 loci are associated with mutant phenotypes that include defective pigmentation, aberrant targeting of lysosomal enzymes, prolonged bleeding, and immunodeficiency, the result of defective biogenesis of cytoplasmic organelles: melanosomes, lysosomes, and various storage granules. Many of these mouse mutants are homologous to the human Hermansky-Pudlak syndrome (HPS), Chediak-Higashi syndrome, and Griscelli syndrome. We have mapped and positionally cloned one of these mouse loci, buff (bf), which has a mutant phenotype similar to that of human HPS. Mouse bf results from a mutation in Vps33a and thus is homologous to the yeast vacuolar protein-sorting mutant vps33 and Drosophila carnation (car). This is the first found defect of the class C vacuole/prevacuole-associated target soluble N-ethylmaleimide-sensitive factor attachment protein receptor (t-SNARE) complex in mammals and the first mammalian mutant found that is directly homologous to a vps mutation of yeast. VPS33A thus is a good candidate gene for a previously uncharacterized form of human HPS.
authors.affiliation: Human Medical Genetics Program, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
authors.forename: Tamio
authors.initials: T
authors.lastname: Suzuki
authors.forename: Naoki
authors.initials: N
authors.lastname: Oiso
authors.forename: Rashi
authors.initials: R
authors.lastname: Gautam
authors.forename: Edward K
authors.initials: EK
authors.lastname: Novak
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Panthier
authors.forename: P G
authors.initials: PG
authors.lastname: Suprabha
authors.forename: Thomas
authors.initials: T
authors.lastname: Vida
authors.forename: Richard T
authors.initials: RT
authors.lastname: Swank
authors.forename: Richard A
authors.initials: RA
authors.lastname: Spritz
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D004330:Drosophila; D029721:Drosophila Proteins; D005136:Eye Proteins; D005816:Genetic Complementation Test; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics*; D006801:Humans; D020460:Melanosomes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D033921:Vesicular Transport Proteins
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005136:Eye Proteins; D011506:Proteins; C424440:VPS33A protein, human; D033921:Vesicular Transport Proteins; C472129:Vps33a protein, mouse; C400361:car protein, Drosophila