Two papers from the same laboratory (Arin et al., page 645 and Cao et al., page 651), describe the use of an inducible gene targeting strategy to develop mouse models for serious human skin diseases. The work has important implications for gene therapy, and also helps to explain why some genetic defects cause a mosaic disease, while others do not. In mosaicism, genetically distinct populations of cells arise from the same lineage in a single tissue; the mechanistic differences between mosaic and nonmosaic genetic diseases are poorly understood.
Arin et al. developed an inducible mouse model for epidermolytic hyperkeratosis (EHK), an autosomal-dominant skin blistering disorder caused by mutations in keratin K1 or K10. When a topical inducer is applied to patches of skin on these mice, the activation of a recombinase produces a local population of mutant epidermal stem...
