Melanocytes and pigmentation are affected in dopachrome tautomerase knockout mice
Melanocytes and pigmentation are affected in dopachrome tautomerase knockout mice
复制标题
DOI：
10.1128/mcb.24.8.3396-3403.2004
复制
发表时间：
2004-04-01
影响因子：
5.3
通讯作者：
Beermann, F
中科院分区：
文献类型：
--
作者：
Guyonneau, L;Murisier, F;Beermann, F
酪氨酸酶家族包括三个成员，酪氨酸酶（Tyr）、酪氨酸酶相关蛋白1（Tyrp 1）和多巴色素互变异构酶（Dct）。已知Tyr和Tyrp 1基因座的突变和缺失，由于缺乏酶或细胞内错误定位，表型影响毛色。在Dct基因座，已知导致色素沉着表型的三个突变。然而，这些突变不是无效突变，因此我们着手通过去除小鼠Dct基因的外显子1在Dct基因座处产生无效等位基因。缺乏Dct [Dct（tm 1（cre）Bee）]的小鼠缺乏Dct mRNA和多巴色素互变异构酶蛋白。它们是有活力的，并且在Dct表达部位如皮肤、视网膜色素上皮或脑中不显示任何异常。然而，小鼠表现出稀释的毛色表型，这是由于毛发中黑色素含量减少。来自Dct敲除小鼠的原代黑素细胞在培养物中存活，并且显示酪氨酸酶和酪氨酸酶相关蛋白1的正态分布。与敲除相比，板状突变（Dct（slt）/Dct（slt））具有更少的黑色素并且严重影响原代黑素细胞的生长。总之，我们已经在小鼠中产生了Dct基因的敲除，其影响仅限于色素产生和毛色。
The tyrosinase family comprises three members, tyrosinase (Tyr), tyrosinase-related protein 1 (Tyrp1), and dopachrome tautomerase (Dct). Null mutations and deletions at the Tyr and Tyrp1 loci are known and phenotypically affect coat color due to the absence of enzyme or intracellular mislocalization. At the Dct locus, three mutations are known that lead to pigmentation phenotype. However, these mutations are not null mutations, and we therefore set out to generate a null allele at the Dct gene locus by removing exon 1 of the mouse Dct gene. Mice deficient in Dct [Dct(tm1(cre)Bee)] lack Dct mRNA and dopachrome tautomerase protein. They are viable and do not show any abnormalities in Dct-expressing sites such as skin, retinal pigment epithelium, or brain. However, the mice show a diluted coat color phenotype, which is due to reduced melanin content in hair. Primary melanocytes from Dct knockout mice are viable in culture and show a normal distribution of tyrosinase and tyrosinase-related protein 1. In comparison to the knockout, the slaty mutation (Dct(slt)/Dct(slt)) has less melanin and affects growth of primary melanocytes severely. In summary, we have generated a knockout of the Dct gene in mice with effects restricted to pigment production and coat color.