RRC ID 32745
Author Fukamachi S, Shimada A, Shima A.
Title Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka.
Journal Nat Genet
Abstract Pigmentation of the skin is of great social, clinical and cosmetic significance. Several genes that, when mutated, give rise to altered coat color in mice have been identified; their analysis has provided some insight into melanogenesis and human pigmentation diseases. Such analyses do not, however, fully inform on the pigmentation of lower vertebrates because mammals have only one kind of chromatophore, the melanocyte. In contrast, the medaka (a small, freshwater teleost) is a suitable model of the lower vertebrates because it has all kinds of chromatophores. The basic molecular genetics of fish are known and approximately 70 spontaneous pigmentation mutants have been isolated. One of these, an orange-red variant, is a homozygote of a well-known and common allele, b, and has been bred for hundreds of years by the Japanese. Here, we report the first successful positional cloning of a medaka gene (AIM1): one that encodes a transporter that mediates melanin synthesis. The protein is predicted to consist of 12 transmembrane domains and is 55% identical to a human EST of unknown function isolated from melanocytes and melanoma cells. We also isolated a highly homologous gene from the mouse, indicating a conserved function of vertebrate melanogenesis. Intriguingly, these proteins have sequence and structural similarities to plant sucrose transporters, suggesting a relevance of sucrose in melanin synthesis. Analysis of AIM1 orthologs should provide new insights into the regulation of melanogenesis in both teleosts and mammals.
Volume 28(4)
Pages 381-5
Published 2001-8-1
DOI 10.1038/ng584
PII ng584
PMID 11479596
MeSH Animals Apiaceae Carrier Proteins / biosynthesis Carrier Proteins / genetics* Carrier Proteins / metabolism Chromosome Mapping Crystallins DNA Mutational Analysis Humans Melanins / genetics* Melanins / metabolism* Membrane Proteins Membrane Transport Proteins* Mice Molecular Sequence Data Oryzias / genetics* Plant Proteins / genetics Protein Structure, Tertiary / genetics Sequence Alignment Sequence Homology, Amino Acid Skin Pigmentation / genetics Symporters
IF 27.605
Times Cited 162
Medaka MT7 MT13 MT72 IB176 IB178