International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


Oral Presentation

Wednesday 20 November

11:00 - 11:15 HRS

MICROARRAY EXPRESSION PROFILING APPLIED TO GENES FOR NEURAL CREST DEVELOPMENT IDENTIFIES RAB38, THE GENE MUTATED IN CHOCOLATE MICE

S. Loftus
National Human Genome Research Institute , NIH

Co-Authors: Larson D, Antonellis A, Baxter L, Wolfsberg T, Pavan W.
Institutions: National Human Genome Research Institute, National Institutes of Health

Mouse pigmentation mutants are valuable for identifying genes involved in neural crest/melanocyte (NC/M) development, and have been useful in gaining a better understanding of human disorders stemming from the NC/M lineage.  However, the genes responsible for the majority of the ~100 pigmentation mutants remain unknown and uncharacterized.  Thus, we have applied a large scale genomic approach to identify the genes involved in NC/M development.  Melanoma samples that varied in pigmentation intensity were hybridized to a custom melanocyte microarray and resulting expression profiles were clustered.  A pigmentation associated cluster of 68 genes was selected based upon the similarity of the profiles with 7 mouse pigmentation mutant genes.  A second "neural crest" cluster contains 72 genes with expression profiles similar to the early neural crest genes Sox10, Ednrb, Mitf and Slug.  Initial analysis of these genes has correlated genomic locations relative to regions of linkage for mouse mutant phenotypes, and evaluation of expression during development using in situ at E11.5 and E9.5.  From this analysis we identified Rab38 as the gene affected in the chocolate mouse.  We demonstrate that Rab38 co-localizes with pigmented melanosomes, and implicate Rab38 in the regulation of proper trafficking of TYRP1 to pigmented melanosomes.  This approach provides a paradigm for combining the resources from the genome project with developmental biology to rapidly identify genes important in the NC/M lineage.


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