STRUCTURE OF THE MOUSE TYROSINASE-RELATED PROTEIN-2 DOPACHROME TAUTOMERASE (TYRP2 DCT) GENE AND SEQUENCE OF 2 NOVEL SLATY ALLELES/

We have isolated the eight exons and 5' and 3' flanking regions of the mouse tyrosinase-related protein-2 (dopachrome tautomerase) gene (Tyr p2/Dct), which is mutated in slaty mice. The gene has a structure that is considerably different from those of other tyrosinase family membe rs in both the number and the position of introns, consistent with the suggestion that the divergence of the family represents an ancient ge ne duplication. We also identify in the 5' flanking DNA an 11-bp eleme nt, the M-box, conserved in other tyrosinase family genes. We have cha racterized point mutations in two slaty alleles recently identified at the Jackson Laboratory: slaty-2J (slt(2J)) has a similar phenotype to the original slaty (slt) mutation, and slaty light (Slt(lt)), which h as a more severe effect and is semidominant. We suggest that the slaty -light phenotype is a result of the failure of the enzyme to be correc tly targeted to its normal location on the inner face of the melanosom al membrane. (C) 1995 Academic Press, Inc.