A NON-EPISTATIC INTERACTION OF AGOUTI AND EXTENSION IN THE FOX, VULPES-VULPES

Agouti and extension are two genes that control the production of yell ow-red (phaeomelanin) and brown-black (eumelanin) pigments in the mamm alian coat(1). Extension encodes the melanocyte-stimulating hormone re ceptor (MC1R)(2,3) while agouti encodes a peptide antagonist of the re ceptor(4-6). In the mouse, extension is epistatic to agouti(7,8), henc e dominant mutants of the MC1R encoding constitutively active receptor s are not inhibited by the agouti antagonist, and animals with dominan t alleles of both loci remain darkly pigmented, In the fox the propose d extension locus is not epistatic to the agouti locus(9,10). We have cloned and characterized the MC1R and the agouti gene in coat colour v ariants of the fox (Vulpes vulpes). A constitutively activating C125R mutation in the MC1R was found specifically in darkly pigmented animal s carrying the Alaska Silver allele (E(A)). A deletion in the first co ding exon of the agouti gene was found associated with the proposed re cessive allele of agouti in the darkly pigmented Standard Silver fox ( aa). Thus, as in the mouse, dark pigmentation can be caused by a const itutively active MC1R, or homozygous recessive status at the agouti lo cus. Our results, demonstrating the presence of dominant extension all eles in foxes with significant red coat colouration, suggest the abili ty of the fox agouti protein to counteract the signalling activity of a constitutively active fox MC1R.