De. Granholm et al., AGOUTI ALLELES INFLUENCE THIOL CONCENTRATIONS IN HAIR-FOLLICLES AND EXTRAFOLLICULAR TISSUES OF MICE (A(Y) A,A(WJ)/A(WJ),A/A)/, Pigment cell research, 8(6), 1995, pp. 302-306
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.