Deregulation of ORMDL3 expression induces stress responses and modulates repair pathways

The asthma-susceptibility gene ORMDL3 is an ER transmembrane protein previously associated with sphingolipid metabolism, the unfolded protein response, Ca2+ homeostasis, T-cell activation, and antiviral responses. However, the functional relevance of ORMDL3 in asthma pathogenesis remains elusive. Using the fruit fly Drosophila melanogaster as a model, we mimicked the situation found in patients at risk for asthma by increasing the expression of ormdl, the sole Drosophila homolog of ORMDL3, in the airway epithelium. Although ormdl overexpression did not overtly affect epithelial integrity, it increased the suscep…