Phenotypic rescue of mutant brown melanocytes by a retrovirus carrying a wild-type tyrosinase-related protein gene.
A mouse cDNA for the developmentally controlled, melanocyte-specific protein, tyrosinase-related protein 1 (TRP-1), was previously cloned and reported to show genetic linkage with the coat-colour locus brown (b) on mouse chromosome 4. The cDNA has been inserted into a retroviral vector derived from Moloney murine leukaemia virus, under the control of the human histone H4 promoter. This vector was used to infect melanocytes of the immortal line melan-b, which are homozygous for the b mutation and which display light brown pigmentation in culture. Infected cultures containing between 0.2 and 2 copies of provirus per cell displayed an altered phenotype: 20-50% of cells now had the black to dark brown colour characteristic of cultured wild-type (Black, B/B) mouse melanocytes. Thus the TRP-1 gene complements the brown mutation. We conclude that TRP-1 is the product of the wild-type b-locus.
Bennett
D C
DC
Department of Anatomy, St George's Hospital Medical School, London, UK.
Huszar
D
D
Laipis
P J
PJ
Jaenisch
R
R
Jackson
I J
IJ
D000818:Animals; D002478:Cells, Cultured; D005822:Genetic Vectors; D008543:Melanins / Q000235:genetics*; D008544:Melanocytes / Q000378:metabolism*; D008562:Membrane Glycoproteins; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics*; D010088:Oxidoreductases; D010641:Phenotype; D010703:Phorbol Esters / Q000494:pharmacology; D011506:Proteins / Q000235:genetics*; D014162:Transfection
D008543:Melanins; D008562:Membrane Glycoproteins; D010703:Phorbol Esters; D011506:Proteins; D010088:Oxidoreductases; C489799:TYRP1 protein, human; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1