The mouse tyrosinase (Tyr) gene enhancer was fused to the Tyr promoter region to produce a 6.1-kb regulatory element driving the expression of a cDNA encoding a stabilized form of beta-catenin in which Ser33, Ser37, Ser45, and Thr41 were replaced by alanines (A33, A37, A41, A45). A nuclear localization signal (nls) and EGFP sequences were fused in frame to the 3' end of the mutated beta-catenin cDNA. An SV40 small T-antigen splice site and polyadenylation sequence were added to the 3' end of the construct to produce Tyr::beta-cat-mut-nls-egfp (bcatsta). This expression vector produces a constitutively activated nuclear form of the protein that is comparable in its activity to the mutated form of beta-catenin found in melanomas and other cancers. The transgene was confirmed to be specifically expressed in cells of the melanocyte lineage. Two independent lines (lines 1 and 2) were generated, both presenting a hypopigmented coat color phenotype. The level of transgene expression in melanocytes cultured from newborn skin was ~10% and 5% of that of the endogenous protein in lines 1 and 2, respectively. The lines are pooled, as denoted by the pound (#) sign. (J:127315)
Basic Information
Insertion, Nucleotide substitutions
Legend:
cx: complex: > 1 genome feature ot: other: hemizygous, indeterminate,... (F): Female
(M): Male
N: normal phenotype
(#): related diseases count