DROSOPHILA MELANOGASTER MINIFLY MUTANTS: A MODEL SYSTEM FOR THE STUDY OF THE MOLECULAR BASIS OF THE X-LINKED DYSKERATOSIS CONGENITA

DKC1, the gene responsible for the X- linked dyskeratosis disease (DC), belongs to a highly conserved gene family whose Drosophila member is the minifly (mfl) gene. Since molecular and genetic characterisation of Drosophila mfl mutants has concretely anticipated the results only recently obtained in DKC1 mutant mice, we believe that further characterization of the Drosophila gene might speed the understanding of the molecular basis of the DC disease. Specifically, we will perform a set of experiments focused to characterise the bulk of alternative products derived from the mfl gene, whose structure currently appears to be much more complex than previously suspected. Our experiments will be focused on the study of an alternative product of the gene that accumulates specifically in females and is maternally provided to the developing embryos. The functional relevance of this product is outlined by the observation that a product of similar size and expression profile is produced also by human and mice DKC1 genes. Since in adults this product is not expressed ubiquitously, its structure may help to understand why the damages observed in DC patients are essentially restricted to only certain tissues. Moreover, on the light of notion that only 50% of mutations present in DC patients lie within the DKC1 product so far characterised, there is a likehood that some mutations may map within this alternative product, whose structure is so far unknown.