title: Mutation of melanosome protein RAB38 in chocolate mice.
abstract: Mutations of genes needed for melanocyte function can result in oculocutaneous albinism. Examination of similarities in human gene expression patterns by using microarray analysis reveals that RAB38, a small GTP binding protein, demonstrates a similar expression profile to melanocytic genes. Comparative genomic analysis localizes human RAB38 to the mouse chocolate (cht) locus. A G146T mutation occurs in the conserved GTP binding domain of RAB38 in cht mice. Rab38(cht)/Rab38(cht) mice exhibit a brown coat similar in color to mice with a mutation in tyrosinase-related protein 1 (Tyrp1), a mouse model for oculocutaneous albinism. The targeting of TYRP1 protein to the melanosome is impaired in Rab38(cht)/Rab38(cht) melanocytes. These observations, and the fact that green fluorescent protein-tagged RAB38 colocalizes with end-stage melanosomes in wild-type melanocytes, suggest that RAB38 plays a role in the sorting of TYRP1. This study demonstrates the utility of expression profile analysis to identify mammalian disease genes.
authors.affiliation: Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Stacie K
authors.initials: SK
authors.lastname: Loftus
authors.forename: Denise M
authors.initials: DM
authors.lastname: Larson
authors.forename: Laura L
authors.initials: LL
authors.lastname: Baxter
authors.forename: Anthony
authors.initials: A
authors.lastname: Antonellis
authors.forename: Yidong
authors.initials: Y
authors.lastname: Chen
authors.forename: Xufeng
authors.initials: X
authors.lastname: Wu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Michael
authors.initials: M
authors.lastname: Bittner
authors.forename: John A
authors.initials: JA
authors.lastname: Hammer
authors.forename: William J
authors.initials: WJ
authors.lastname: Pavan
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002874:Chromosome Mapping; D020869:Gene Expression Profiling; D006801:Humans; D008544:Melanocytes / Q000502:physiology; D020460:Melanosomes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D010088:Oxidoreductases; D010859:Pigmentation Disorders / Q000235:genetics*; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000502:physiology
chemical_list: D008562:Membrane Glycoproteins; D010088:Oxidoreductases; C489799:TYRP1 protein, human; C079621:Tyrp1 protein, mouse; C412058:RAB38 protein, human; C498786:Rab38 protein, mouse; D020691:rab GTP-Binding Proteins