Krauss Jana, Geiger-Rudolph Silke, Koch Iris, Nüsslein-Volhard Christiane, Irion Uwe
Max Planck Institute for Developmental Biology, Tübingen, Germany.
Pigment Cell Melanoma Res. 2014 Sep;27(5):827-30. doi: 10.1111/pcmr.12272. Epub 2014 Jul 3.
Melanin biosynthesis in vertebrates depends on the function of three enzymes of the tyrosinase family, tyrosinase (Tyr), tyrosinase-related protein 1 (Tyrp1), and dopachrome tautomerase (Dct or Tyrp2). Tyrp1 might play an additional role in the survival and proliferation of melanocytes. Here, we describe a mutation in tyrp1A, one of the two tyrp1 paralogs in zebrafish, which causes melanophore death leading to a semi-dominant phenotype. The mutation, an Arg->Cys change in the amino-terminal part of the protein, is similar to mutations in humans and mice where they lead to blond hair (in melanesians) or dark hair with white bases, respectively. We demonstrate that the phenotype in zebrafish depends on the presence of the mutant protein and on melanin synthesis. Ultrastructural analysis shows that the melanosome morphology and pigment content are altered in the mutants. These structural changes might be the underlying cause for the observed cell death, which, surprisingly, does not result in patterning defects.
脊椎动物体内的黑色素生物合成依赖于酪氨酸酶家族的三种酶的功能，即酪氨酸酶（Tyr）、酪氨酸酶相关蛋白1（Tyrp1）和多巴色素互变异构酶（Dct或Tyrp2）。Tyrp1可能在黑素细胞的存活和增殖中发挥额外作用。在此，我们描述了斑马鱼中两个tyrp1旁系同源基因之一tyrp1A的一个突变，该突变导致黑素细胞死亡，从而产生半显性表型。该突变是蛋白质氨基末端部分的精氨酸（Arg）突变为半胱氨酸（Cys），类似于人类和小鼠中的突变，在人类中该突变导致金发（在美拉尼西亚人当中），在小鼠中则导致带白色基部的深色毛发。我们证明斑马鱼中的表型取决于突变蛋白的存在以及黑色素合成。超微结构分析表明，突变体中的黑素体形态和色素含量发生了改变。这些结构变化可能是观察到的细胞死亡的根本原因，令人惊讶的是，这并未导致模式缺陷。
