Article: article from journal or magazin.
Melanocytes and pigmentation are affected in dopachrome tautomerase knockout mice.
Molecular and Cellular Biology
Publication types: Journal Article
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.
Animals, Brain/cytology, Brain/metabolism, Cells, Cultured, Eye/cytology, Eye/metabolism, Gene Targeting, Intramolecular Oxidoreductases/genetics, Intramolecular Oxidoreductases/metabolism, Melanocytes/cytology, Melanocytes/metabolism, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Monophenol Monooxygenase/genetics, Monophenol Monooxygenase/metabolism, Mutation, Oxidoreductases, Phenotype, Pigmentation/physiology, Proteins/genetics, Proteins/metabolism, Skin/cytology, Skin/metabolism
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