title: A dominant mutation in tyrp1A leads to melanophore death in zebrafish.
abstract: 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.
authors.affiliation: Max Planck Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Krauss
authors.forename: Silke
authors.initials: S
authors.lastname: Geiger-Rudolph
authors.forename: Iris
authors.initials: I
authors.lastname: Koch
authors.forename: Christiane
authors.initials: C
authors.lastname: Nüsslein-Volhard
authors.forename: Uwe
authors.initials: U
authors.lastname: Irion
mesh_terms: D000818:Animals; D016923:Cell Death; D002462:Cell Membrane / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology*; D008562:Membrane Glycoproteins; D009154:Mutation; D010088:Oxidoreductases; D010641:Phenotype; D010670:Phenylthiourea / Q000737:chemistry; D010858:Pigmentation; D012038:Regeneration; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D008543:Melanins; D008562:Membrane Glycoproteins; D029961:Zebrafish Proteins; D010670:Phenylthiourea; D010088:Oxidoreductases; C547074:Tyrp1b protein, zebrafish; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase
keywords: melanin; melanophore; pigmentation; tyrosinase-related protein 1; zebrafish