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PMID: 11917121 Published · ppublish English Journal Article

Mutation of melanosome protein RAB38 in chocolate mice.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 7 ·2002-04-02 ·Pages 4471-6

Loftus SK, Larson DM, Baxter LL, Antonellis A, Chen Y, Wu X, Jiang Y, Bittner M, Hammer JA, Pavan WJ

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.

MeSH Terms
Animals Base Sequence Cells, Cultured Chromosome Mapping Gene Expression Profiling Humans Melanocytes/physiology Melanosomes/metabolism Membrane Glycoproteins/genetics,metabolism Mice Mice, Inbred C57BL Molecular Sequence Data Mutation Oxidoreductases Pigmentation Disorders/genetics rab GTP-Binding Proteins/genetics,physiology
Chemicals
Membrane Glycoproteins Oxidoreductases TYRP1 protein, human Tyrp1 protein, mouse RAB38 protein, human Rab38 protein, mouse rab GTP-Binding Proteins
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Loftus Stacie K
Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Larson Denise M
Baxter Laura L
Antonellis Anthony
Chen Yidong
Wu Xufeng
Jiang Yuan
Bittner Michael
Hammer John A
Pavan William J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.072087599
Published
2002-04-02
Epub
2002-00-26
Pages
4471-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC123672
Subset
IM
Databases
GENBANK
AF448441, AF448442, AF448443, AY062237
External Links
PubMed source DOI: 10.1073/pnas.072087599 PMC Full Text View journal details
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