title: Homologous pigmentation mutations in human, mouse and other model organisms.
abstract: 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.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK. ian.jackson@hgu.mrc.ac.uk
authors.forename: I J
authors.initials: IJ
authors.lastname: Jackson
mesh_terms: D054366:Agouti Signaling Protein; D000595:Amino Acid Sequence; D000818:Animals; D030342:Genetic Diseases, Inborn / Q000235:genetics; D014644:Genetic Variation; D006200:Hair Color / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008543:Melanins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010858:Pigmentation / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D018043:Receptors, Corticotropin / Q000737:chemistry / Q000235:genetics*; D044101:Receptors, Melanocortin; D016415:Sequence Alignment
chemical_list: C515182:ASIP protein, human; D054366:Agouti Signaling Protein; D036341:Intercellular Signaling Peptides and Proteins; D008543:Melanins; D011506:Proteins; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C515183:a protein, mouse