Molecular characterization of the mouse tyrosinase gene: pigment cell-specific expression in transgenic mice

Friedrich Beermann
1992
Journal paper

Abstract

Tyrosinase is the key enzyme in melanin synthesis, and is expressed in the pigment epithelium of the retina, a cell layer derived from the optic cup; and in neural crest-derived melanocytes of skin, hair follicle, choroid, and iris. The tyrosinase gene has been cloned and shown to map to the well-characterized c-locus (albino locus) of the mouse. Subsequent studies demonstrated that a functional tyrosinase minigene was able to rescue the albino phenotype in transgenic mice. The transgene was expressed in a cell type-specific manner in skin and eye. During development of the mouse, the tyrosinase gene is expressed in the pigment epithelium of the retina as early as day 10.5 of gestation. In the hair follicle, tyrosinase gene expression is detected from day 16.5 onwards. This cell-type-specific expression is largely reproduced in transgenic mice. Our results suggest that sequences in the immediate vicinity of the mouse tyrosinase gene are sufficient to provide cell type-specificity and developmental regulation in melanocytes and the pigment epithelium.

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Friedrich Beermann
1992
Journal paper

Abstract

Official source

https://infoscience.epfl.ch/record/115431?ln=en

About this result

Related concepts (11)

A mouse (: mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species i

Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal ep

Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. The enzyme is mainly involved in two distinct reactions of melanin synthesis otherwise known as the

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Related publications (25)

Related publications

Pigment in mammals is produced in melanocytes of the skin derived from the neural crest and in the pigmented epithelial cells of the retina derived from the optic cup. Tyrosinase (monophenol, L-dopa:oxygen oxidoreductase, EC 1.14.18.1) is regarded as the key enzyme in pigment synthesis in both these cell types. In this study, we have investigated the temporal regulation of expression of the tyrosinase gene during early eye development and in the developing hair follicle of the mouse by in situ hybridization and have asked whether transgenes would precisely mimick this pattern. We show that the mouse tyrosinase gene is expressed in the pigment epithelium of the retina as early as day 10.5 of gestation. In the hair follicle, tyrosinase gene expression in melanocytes is detected from day 16.5 onwards. This cell type-specific and temporal expression is largely reproduced in transgenic mice carrying a tyrosinase minigene. Our results suggest that sequences in the immediate vicinity of the mouse tyrosinase gene are sufficient to provide cell-type specificity and developmental regulation in melanocytes and in the pigment epithelium.

1992

The mouse tyrosinase promoter is sufficient for expression in melanocytes and in the pigmented epithelium of the retina

Friedrich Beermann

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.

1991

Tyrosinase is one of the key enzymes in mammalian melanin synthesis. The pigment is produced in two different cell types: the pigmented epithelial cell of the retina, and the melanocyte, a cell of neural-crest origin. We recently showed that a fusion gene between regulatory sequences of tyrosinase gene (tyr) and the beta-galactosidase gene (lacZ), when introduced into transgenic mice, resulted in embryonic expression in presumptive pigment cells but also in cells populations along the entire neural tube. This expression in the developing brain was striking, and we therefore asked whether this would still be detectable after birth. Transgenic mice carrying the tyr-lacZ fusion gene showed beta-galactosidase expression in adult brain. On Western blots, we detected tyrosinase-specific bands of 65-68 kDa in brain and eye. Using an affinity-purified antibody, we showed that detection of tyrosinase is specific and competed off by the presence of the cognate tyrosinase-derived peptide. However, neither tyrosine hydroxylase nor Dopa oxidase activity were detected in protein extracts of brain. We therefore suggest that tyrosinase is present in brain but either not functional or catalyzing different reactions compared to pigment cells.

1996