Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka
Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka
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DOI：
10.1038/ng584
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发表时间：
2001-08-01
期刊：
影响因子：
30.8
通讯作者：
Shima, A
中科院分区：
文献类型：
--
作者：
Fukamachi, S;Shimada, A;Shima, A
皮肤色素沉着具有重要的社会、临床和美容意义。已经鉴定出几种基因，当突变时，会引起小鼠毛色的改变;它们的分析（1-6）为黑素生成和人类色素沉着疾病提供了一些见解。然而，这样的分析并不能完全说明低等脊椎动物的色素沉着，因为哺乳动物只有一种色素细胞，即黑素细胞。相比之下，青鳉（一种小型的淡水硬骨鱼）是低等脊椎动物的合适模型，因为它有各种各样的色素细胞。鱼类的基本分子遗传学是已知的（7，8），并且已经分离出大约70种自发色素沉着突变体（9）。其中一种是橙红色的变异体，它是一种众所周知的常见等位基因B的纯合子，日本人已经培育了几百年。在这里，我们报告的第一个成功的位置克隆的青鳉基因（AIM 1）：一个编码转运介导黑色素合成。预测该蛋白质由12个跨膜结构域组成，并且与从黑素细胞和黑素瘤细胞分离的未知功能的人EST具有55%的同一性。我们还从小鼠中分离出一个高度同源的基因，表明脊椎动物黑素生成的保守功能。有趣的是，这些蛋白质与植物蔗糖转运蛋白具有序列和结构相似性，表明蔗糖与黑色素合成相关。AIM 1同源基因的分析应该为硬骨鱼和哺乳动物的黑素生成调控提供新的见解。
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(1-6) 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 known(7,8) and approximately 70 spontaneous pigmentation mutants have been isolated(9). 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.