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Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka

Nature Genetics volume 28, pages 381–385 (2001)Cite this article

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 analysis1,2,3,4,5,6 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 known7,8 and approximately 70 spontaneous pigmentation mutants have been isolated9. 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.

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Figure 1: Phenotypes of wildtype and b-locus mutants. From top to bottom: wildtype (B/B), b (b/b) and bg8 (bg8/bg8).
Figure 2: Genetic and physical map of the b mutation candidate interval.
Figure 3: Sequence alignment of medaka (HNI strain), human and mouse AIM-1.
Figure 4: Mutations in AIM1.
Figure 5: Expression of AIM1.
Figure 6: Amino-acid sequence alignment of medaka B (HNI strain) and Apium graveolens sucrose transporter (agSUT1).

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Acknowledgements

Authors thank H. Hori at the Nagoya University for the BAC genomic library; K. Ozato and Y. Wakamatsu at the Nagoya University for the i6/i6 strain; K. Inohaya at the Tokyo Institute of Technology for advice on in situ hybridization; K. Kator at the University of Tokyo for albino (ddY) mice; and K. Naruse, H. Mitani, and M. Nonaka at the University of Tokyo for their continuous advice on our experiments and comments on the manuscript. This research was supported by a Grant-in-Aid from the Ministry of Education, Science, Sports and Culture, Japan, and by the Ministry of Health and Welfare, Japan (scientific research on priority areas, area number 813).

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Authors and Affiliations

  1. Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa-no-ha 5-1-5, Kashiwa-shi, 277-0882, Chiba-ken, Japan

    Shoji Fukamachi & Akihiro Shima

  2. Department of Biological Sciences, Laboratory of Radiation Biology, School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-0033, Tokyo, Japan

    Atsuko Shimada & Akihiro Shima

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  1. Shoji Fukamachi
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Correspondence to Shoji Fukamachi.

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Fukamachi, S., Shimada, A. & Shima, A. Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka. Nat Genet 28, 381–385 (2001). https://doi.org/10.1038/ng584

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