Budd P S, Jackson I J
Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom.
Genomics. 1995 Sep 1;29(1):35-43. doi: 10.1006/geno.1995.1212.
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.
我们已经分离出了小鼠酪氨酸酶相关蛋白2（多巴色素互变异构酶）基因（Tyrp2/Dct）的8个外显子以及5'和3'侧翼区域，该基因在石板色小鼠中发生了突变。该基因的结构在数量和内含子位置上与其他酪氨酸酶家族成员的结构有很大不同，这与该家族的分化代表着一次古老的基因复制的观点一致。我们还在5'侧翼DNA中鉴定出了一个11碱基对的元件，即M盒，它在其他酪氨酸酶家族基因中是保守的。我们对最近在杰克逊实验室鉴定出的两个石板色等位基因中的点突变进行了表征：石板色-2J（slt2J）与原始的石板色（slt）突变具有相似的表型，而石板色浅色（Sltlt）具有更严重的影响且是半显性的。我们认为石板色浅色表型是由于该酶未能正确靶向到黑素体膜内表面的正常位置所致。
