Abstract
Junctional epidermolysis bullosa (JEB) caused by loss of function variants in genes encoding the skin basement membrane proteins Laminin 332 (Lam332), type XVII collagen or integrin α6β4, effects patients from birth with severe blistering eventually leading to scarring and early lethality. Here we have optimised a previously published JEB eKO model with weekly tamoxifen intraperitoneal injections resulting in a more controllable and severe model. Due to the titratable dosing this model now recapitulates both early and advanced stages of the human disease, strengthening its use in therapeutic studies. The gradual loss of Lam-α3 in the skin of the mouse through weekly injections lead to generalised blistering and fibrotic dermal changes in multiple skin sites by week 12 post-tamoxifen. Our findings demonstrate the usefulness of optimising tamoxifen induction in Cre-loxP mouse models of extracellular matrix proteins, an approach that could be applicable to other emerging inducible transgenic disease models to improve their ability to mimic the human disease phenotype.
Published Version
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