HOMOLOGOUS PIGMENTATION MUTATIONS IN HUMAN, MOUSE AND OTHER MODEL ORGANISMS

Mouse coat colour genes have long been studied as a paradigm for genet ic interactions in development, A number of these genes have been clon ed and most correspond to human genetic disease loci. The proteins enc oded by these genes include transcription factors, receptor tyrosine k inases and growth factors, G-protein coupled receptors and their ligan ds, membrane proteins, structural proteins and enzymes, Many of the mu tations 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 mous e or human, and I focus on three particular systems, One family of gen es, including LYST and HPS/ep, shows the relationship between melanoso mes 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 e xpressed only on melanocytes, but mutations that cause overexpression of agouti protein, an antagonist of the receptor, result in obesity, a nd highlight a role of melanocortins in weight homoeostasis.