Jackson I J
MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
Hum Mol Genet. 1997;6(10):1613-24. doi: 10.1093/hmg/6.10.1613.
Mouse coat colour genes have long been studied as a paradigm for genetic interactions in development. A number of these genes have been cloned and most correspond to human genetic disease loci. The proteins encoded by these genes include transcription factors, receptor tyrosine kinases and growth factors, G-protein coupled receptors and their ligands, membrane proteins, structural proteins and enzymes. Many of the mutations have pleiotropic effects, indicating that these proteins play a wider role in developmental or cellular processes. In this review I tabulate the available data on all pigmentation genes cloned from mouse or human, and I focus on three particular systems. One family of genes, including LYST and HPS/ep, shows the relationship between melanosomes and lysosomes. The G-protein coupled receptor, endothelin receptor-B, and its ligand, endothelin-3, are required for the development of both melanocytes and enteric neurons. The melanocortin-1 receptor is expressed only on melanocytes, but mutations that cause overexpression of agouti protein, an antagonist of the receptor, result in obesity, and highlight a role of melanocortins in weight homoeostasis.
小鼠毛色基因长期以来一直作为发育中基因相互作用的范例进行研究。其中许多基因已被克隆，且大多数与人类遗传疾病位点相对应。这些基因编码的蛋白质包括转录因子、受体酪氨酸激酶和生长因子、G蛋白偶联受体及其配体、膜蛋白、结构蛋白和酶。许多突变具有多效性，表明这些蛋白质在发育或细胞过程中发挥着更广泛的作用。在这篇综述中，我将列出从小鼠或人类克隆的所有色素沉着基因的现有数据，并重点关注三个特定系统。一类基因，包括LYST和HPS/ep，显示了黑素小体与溶酶体之间的关系。G蛋白偶联受体内皮素受体-B及其配体内皮素-3是黑素细胞和肠神经元发育所必需的。黑皮质素-1受体仅在黑素细胞上表达，但导致该受体拮抗剂刺鼠蛋白过度表达的突变会导致肥胖，并突出了黑皮质素在体重稳态中的作用。
