Structure of the mouse tyrosinase-related protein-2/dopachrome tautomerase (Tyrp2/Dct) gene and sequence of two 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 (Tyrp2/Dct), which is mutated in slaty mice. The gene has a structure that is considerably different from those of other tyrosinase family members in both the number and the position of introns, consistent with the suggestion that the divergence of the family represents an ancient gene duplication. We also identify in the 5' flanking DNA an 11-bp element, the M-box, conserved in other tyrosinase family genes. We have characterized point mutations in two slaty alleles recently identified at the Jackson Laboratory: slaty-2J (slt2J) has a similar phenotype to the original slaty (slt) mutation, and slaty light (Sltlt), which has 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 correctly targeted to its normal location on the inner face of the melanosomal membrane.
Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom.
P S
PS
Budd
I J
IJ
Jackson
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D017931:DNA Primers; D005091:Exons; D015698:Genomic Library; D006801:Humans; D019746:Intramolecular Oxidoreductases; D007438:Introns; D007535:Isomerases / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000235:genetics*; D005810:Multigene Family; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid
D017931:DNA Primers; D014442:Monophenol Monooxygenase; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase