Mutation of Melanosome Protein RAB38 in chocolate Mice

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. Compara...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2002-04, Vol.99 (7), p.4471-4476
Main Authors: Loftus, Stacie K., Larson, Denise M., Baxter, Laura L., Antonellis, Anthony, Chen, Yidong, Wu, Xufeng, Jiang, Yuan, Bittner, Michael, Hammer, John A., Pavan, William J.
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Biological Sciences
Cell lines
Cells, Cultured
Chromosome Mapping
Complementary DNA
DNA
Exons
Gene Expression Profiling
Genes
Genetic mutation
Genetics
HeLa cells
Humans
Melanocytes
Melanocytes - physiology
Melanosomes
Melanosomes - metabolism
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Mutation
Nucleotides
oculocutaneous albinism
Oxidoreductases
Pigmentation
Pigmentation Disorders - genetics
Proteins
rab GTP-Binding Proteins - genetics
rab GTP-Binding Proteins - physiology
RAB38 gene
RAB38 protein
Rodents
TYRP1 protein
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Summary: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. Rab38cht/Rab38chtmice 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 Rab38cht/Rab38chtmelanocytes. 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.072087599