Effect of Altered Copper Metabolism Induced by Mottled Alleles and Diet on Mouse Tyrosinase 1

Summary

An analysis of tyrosinase activity in extracts of hair bulbs from mice bearing alleles at the mottled locus, Mo^br (brindled), and Mo^blo (blotchy), indicates that reduced melanogenesis in mottled mice is associated with restricted availability of copper. Although tyrosinase activity in 35,000g supernatants of hair-bulb homogenates of mottled mice is reduced compared to that of nonmottled controls, addition of copper to the former but not the latter supernatants markedly increases tyrosinase activity as measured in polyacrylamide gel electropherograms (dopa as substrate) or by the Pomerantz radioassay (tyrosine as substrate). Comparable results were obtained when tyrosinase from dietarily copper-deficient hypopigmented mice was assayed by either method. In the electropherograms of dietarily and genetically copper-deficient hair-bulb supernatants, the enhancement of activity is selectively restricted to the T₁ variety of tyrosinase. It is concluded that alleles at the mottled locus influence tyrosinase and consequently melanin pigmentation by acting on melanocytes to reduce copper levels below those necessary to produce a normal complement of functional tyrosinase molecules.