The murine agouti gene regulates the production of eumelanin and phaeomelanin by hair bulb melanocytes. We have identified a new agouti allele, hypervariable yellow ($A\sp{hvy}$), that is responsible for the largest variation in phenotype of all agouti alleles. Mice carrying the $A\sp{hvy}$ allele can range in phenotype from obese with yellow coats, to normal weight with almost pure black coats. We show that the expression of agouti is correlated with the amount of yellow pigment in the coats of A$\sp{hvy}$ mice as well as their weight. Sequencing of 5$\sp\prime$ RACE and genomic PCR products revealed that $A\sp{hvy}$ is the result of an intracisternal A-particle that inserted in an antisense orientation into the 5$\sp\prime$ untranslated exon 1C of agouti. This retrovirus-like element is responsible for deregulating agouti expression in $A\sp{hvy}$ mice; agouti expression is correlated with the methylation state of CpG residues in the IAP LTR as well as in host genomic DNA. We have identified strain-specific differences in the variable expressivity of the $A\sp{hvy}$ phenotype, through crosses of $A\sp{hvy}$ to various inbred strains. To identify genetic factors that can influence the phenotypic variability exhibited by $A\sp{hvy}$ offspring, we performed quantitative trait loci analysis using an F$\sb2$ intercross and a cross of the BXH RI series. We detected QTLs associated with $A\sp{hvy}$ on several chromosomes. Genomic regions on chromosomes 1, 4, 9, and 19 were identified in both crosses. In addition, we report the dependence of phenotypic variability of $A\sp{hvy}$ mice on epigenetic effects originating from differences in the maternal environment. We observed that yellow $A\sp{hvy}$ females tend to produce more yellow offspring than black $A\sp{hvy}$ females of the identical genotype.
