The human homologue of the murine obesity gene, agouti, is expressed in adipose tissue. We have shown that recombinant agouti protein regulates adipocyte lipogenesis and lipolysis coordinately and promotes lipid storage via a Ca(2+)-dependent mechanism in vitro, which may contribute to agouti-induced obesity. However, little is known about agouti's physiologic function in humans. We first studi...

Chronic antagonism of melanocortin receptors by the paracrine-acting agouti gene product induces both yellow fur and a maturity-onset obesity syndrome in mice that ubiquitously express wild-type agouti. Functional analysis of agouti mutations in transgenic mice indicate that the cysteine-rich C terminus, signal peptide, and glycosylation site are required for agouti activity in vivo. In contras...

Agouti is a secreted paracrine factor that regulates pigmentation in hair follicle melanocytes. Several dominant mutations cause ectopic expression of agouti, resulting in a phenotype characterized by yellow fur, adult-onset obesity and diabetes, increased linear growth and skeletal mass, and increased susceptibility to tumors. Humans also produce agouti protein, but the highest levels of agout...

HE action of genes at the agouti locus, in combination with “wild” genes at other color loci, results in coat color phenotypes which range from all black ( a / a ) to all yellow (Ay / ) . Between these two extremes is the agouti phenotype (A/--) which is typically characterized by the presence of a subapical yellow band on an otherwise black hair. These observations indicate that alleles at the...

The mouse mutations mahogany (mg) and mahoganoid (md) are negative modifiers of the Agouti coat color gene, which encodes a paracrine signaling molecule that induces a swithc in melanin synthesis from eumelanin to pheomelanin. Animals mutant for md or mg synthesize very little or no pheomelanin depending on Agouti gene background. The Agouti protein is normally expressed in the skin and acts as...

The agouti locus on mouse chromosome 2 encodes a secreted cysteine-rich protein of 131 amino acids that acts as a molecular switch to instruct the melanocyte to make either yellow pigment (phaeomelanin) or black pigment (eumelanin). Mutations that up-regulate agouti expression are dominant to those causing decreased expression and result in yellow coat color. Other associated effects are obesit...

For decades, geneticists, as well as breeders of “fancy” pets, have been interested in the interaction of the melanocortin 1 receptor locus (Mc1r; also known as melanocyte-stimulating hormone receptor, Mshr) with the Agouti locus because of the array of coat colors that alterations at these loci generate. In the simplest case, a mouse with two wild-type Mc1r alleles and two recessive Agouti all...

Experiments with a strain of black-and-tan mice obtained from an English fancier* 'have shown that these mice contain a hi-therto undescribed gene which is allelomorphic to yellow, agouti, and non-agouti (black}, and: consequently forms a fifth member of this series of multiple allelomorphs. The black-and-tans used are jet black dorsally with a bright yellow belly and retain this coloration thr...

gus (rabbits), Sciurus (squirrels), and Canis (wolves) (reviewed in ref. 1). Much interest has focused on the agouti gene because several dominant mutations result in mice that exhibit adult onset obesity, hyperinsulinemia, and noninsulindependent diabetes. In addition, mice carrying dominant agouti mutations show an increased susceptibility to a variety of spontaneous and/or induced solid tumo...