AGOUTI ALLELES INFLUENCE THIOL CONCENTRATIONS IN HAIR-FOLLICLES AND EXTRAFOLLICULAR TISSUES OF MICE (A(Y) A,A(WJ)/A(WJ),A/A)/

Agouti protein (AP) expression in the wild-type agouti mouse (A(wJ)/A( wJ)) coincides with a switch in hair follicle melanogenesis from black (eumelanin) to yellow (pheomelanin). Ectopic overexpression of AP in the lethal yellow (A(y)/a) mouse cause a pure yellow coat and the leth al yellow syndrome. Thiol concentrations may control the conversion of dopaquinone to pheomelanin in hair follicle melanocytes. Glutathione (GSH) also plays important roles in cellular health and protection. Us ing HPLC, cysteine and GSH were measured in 1) hair follicles, liver a nd serum of A(y)/a, A(wJ)/A(wJ), and ala (black) mice, and pheomelanin phase). Agouti locus alleles influence thiol metabolism in hair folli cles and in other systemic tissues. A(y)/a hair follicles and serum sh owed highest cysteine and lowest GSH levels. A(wJ)/A(wJ) mice showed i ntermediate levels, while ala hair follicles and serum had lowest cyst eine and highest GSH concentrations. In the hair follicle, cysteine (l ikely derived from enzymatic degradation of GSH) appears to be the pri mary pheomelanogenic thiol. Agouti locus alleles may also directly or indirectly affect thiol concentrations in systemic tissues like liver and spleen. Cysteine in spleen extracts showed A(Y)/a > a/a (P < 0.01) . An A(y)-induced imbalance of thiol metabolism (altering GSH concentr ations in multiple tissues) may contribute to the pleiotropic defects of the lethal yellow syndrome.