The mouse tyrosinase promoter is sufficient for expression in melanocytes and in the pigmented epithelium of the retina.
- 1 May 1991
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 88 (9) , 3777-3781
- https://doi.org/10.1073/pnas.88.9.3777
Abstract
The mouse c locus encodes tyrosinase (monophenol monooxygenase; monophenol, L-dopa:oxygen oxidoreductase, EC 1.14.18.1), the key enzyme in melanin synthesis, which is expressed in the pigment epithelium of the retina and in melanocytes derived from the neural crest. To define regulatory regions of the gene that are important for cell type-specific expression, a deletion series of the tyrosinase 5' region was fused to a chloramphenicol acetyltransferase (CAT) reporter gene and electroporated into tyrosinase-expressing and -nonexpressing cell lines. We show that 270 base pairs 5' of the transcriptional start site is sufficient for CAT expression in a human and a mouse melanoma cell line. This 5' flanking fragment, when cloned in the context of a tyrosinase minigene construct and injected into fertilized eggs of an albino mouse strain, is sufficient for cell type-specific expression in mice. The transgenic mice were pigmented in both skin and eyes. In situ hybridization analysis shows that the 270-base-pair regulatory region contains elements sufficient for specific expression of the transgene both in the pigmented epithelial cells of the retina, which are derived from the optic cup, and in neural crest-derived melanocytes.Keywords
This publication has 14 references indexed in Scilit:
- A cyclic AMP response element mediates repression of tyrosine aminotransferase gene transcription by the tissue-specific extinguisher locus Tse-1Cell, 1990
- Conserved cysteine to serine mutation in tyrosinase is responsible for the classical albino mutation in laboratory miceNucleic Acids Research, 1990
- Analysis of Mammalian Pigmentation at the Molecular LevelPigment Cell Research, 1989
- Dwarf mice produced by genetic ablation of growth hormone-expressing cells.Genes & Development, 1988
- Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus.Proceedings of the National Academy of Sciences, 1987
- CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elementsNucleic Acids Research, 1987
- Specific expression of an elastase–human growth hormone fusion gene in pancreatic acinar cells of transgenic miceNature, 1985
- The rapid generation of oligonucleotide-directed mutations at high frequency using phosphorothioate-modified DNANucleic Acids Research, 1985
- Surface antigens of melanocytes and melanomas. Markers of melanocyte differentiation and melanoma subsets.The Journal of Experimental Medicine, 1982
- Cell surface antigens of human malignant melanoma: mixed hemadsorption assays for humoral immunity to cultured autologous melanoma cells.Proceedings of the National Academy of Sciences, 1976