Molecular studies of two genes, Agouti andextension, which determine pigment production and patterning in the domestic dog

Abstract

Most of our current knowledge about mammalian pigmentation and pigment synthesis has come from the mouse. Despite the wealth of information still to be gained from the mouse system, more could be learned by extending mouse genetics into other mammals. An attractive model for pigmentation studies is the domestic dog. The wide variety of pigment patterns in the many breeds provide a deep source for molecular and genetic investigation. The studies presented here include molecular characterization of two genes which play important roles in the pigmentation and pigment patterning of domestic dogs. These results are supported by comparison with similar results from the mouse and other mammalian species. The two genes studied here are the melanocyte receptor for α-MSH, encoded by the extension locus, and the functional antagonist of this receptor, the agouti protein, encoded by the agouti locus. Studies in the mouse system have demonstrated that the α-MSH receptor is required for the production of black pigment (eumelanin) and that the action of the agouti protein is to cause a switch from the synthesis of black pigment to the production of yellow pigment (pheomelanin). Various alleles at the extension locus result in varying amounts of black pigment synthesis by melanocytes in the hair follicle. Molecular characterization of these alleles has identified missense mutations which alter receptor activity and correlate with changes in coat color. In the studies presented here I have identified sequence changes in the gene for the α-MSH receptor in domestic dogs. These changes include four missense mutations which correlate with the dominantly inherited coat color of certain breeds as well as a truncation in the receptor protein which correlates with the recessive yellow coat color. The key regulator of mammalian coat color patterning is the agouti locus. Regional and temporal patterns of agouti expression in the mouse correlate with the production of yellow pigment. Here I present evidence that the domestic dog also expresses agouti and that its expression correlates with pheomelanogenesis. Furthermore, I provide evidence that gene regulatory elements which control the ventral-specific expression of the agouti gene are conserved between canines and mice.