When a lack of gene conservation becomes a plus--fly as a model of Epidermolysis Bullosa Simplex

Bohnekamp J, Cryderman DE, Paululat A, Baccam GC, Wallrath LL, Magin TM. A Drosophila Model of Epidermolysis Bullosa Simplex. J Invest Dermatol. 2015 Aug;135(8):2031-9. PMID: 25830653; PMCID: PMC4519992.

From the abstract: "The blistering skin disorder epidermolysis bullosa simplex (EBS) results from dominant mutations in keratin 5 (K5) or keratin 14 (K14) genes, encoding the intermediate filament (IF) network of basal epidermal keratinocytes. ... Drosophila lacks cytoplasmic IFs, providing a 'null' environment to examine the formation of keratin networks and determine mechanisms by which mutant keratins cause pathology. Here, we report that ubiquitous co-expression of transgenes encoding wild-type human K14 and K5 resulted in the formation of extensive keratin networks in Drosophila epithelial and non-epithelial tissues, causing no overt phenotype. Similar to mammalian cells, treatment of transgenic fly tissues with phosphatase inhibitors caused keratin network collapse, validating Drosophila as a genetic model system to investigate keratin dynamics. Co-expression of K5 and a K14(R125C) mutant that causes the most severe form of EBS resulted in widespread formation of EBS-like cytoplasmic keratin aggregates ... This Drosophila model of EBS is valuable for the identification of pathways altered by mutant keratins and for the development of EBS therapies."