International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


Murisier F
Swiss Institute for Experimental Cancer Research (ISREC)

Co-Authors: Guichard S, Beermann F
Institutions: Swiss Institute for Experimental Cancer Research (ISREC)

Pigment cells are an attractive system to understand the molecular mechanism of cell lineage commitment. They are not essential for viability and they display visible phenotypes (pigmentation). In mammals, pigment cells originate from two different lineages: melanocytes of skin, hair follicle, and uveal tract of the eye originate from the neural crest, whereas cells of the retinal pigmented epithelium (RPE) originate from the optic cup of the developing forebrain. Three pigment cell specific enzymes, forming the tyrosinase-related protein family, are responsible for the melanin production: tyrosinase, TYRP-I and DCT. Within the mouse tyrosinase regulatory region, a S/MAR-containing 3.6 kb enhancer fragment was identified at –15 kb from the transcriptional start site, which was shown to behave as a locus control region (LCR), insulating the transgene from position effects. Previous experiments performed in our lab using lacZ reporter in transgenics have pointed out the following enhancer features: the enhancer is necessary to drive detectable expression in melanocytes, whereas the tyrosinase promoter alone is sufficient in RPE cells; the enhancer does not increase transgene expression in RPE. We have now dissected the 3.6 kb enhancer in small parts and performed transient or stable transfection experiments. A short central part (core-enhancer) showed full enhancer activity in melanocytes and no enhancement in RPE cells. We also pointed out that the enhancer is not restricted to the tyrosinase promoter but keeps its melanocyte specificity when associated with ubiquitous promoters. We are currently using BAC engineering in transgenics to analyse the in vivo enhancer function.

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