This report describes asthma, susceptibility to, ORMDL3-related.
The human gene implicated in this disease is ORMDL-3 (orosomucoid 1-like 3, ORMDL sphingolipid biosynthesis regulator 3). There is one high-ranking ortholog of ORMDL-3 in Drosophila, ORMDL. Multiple alleles have been generated for ORMDL, including an overexpression construct, multiple RNAi targeting constructs, and insertion lines.
Overexpression of Dmel\ORMDL in Drosophila airway epithelia causes a reduction in the number and size of branches of termina tracheal cells (FBbt:00005053), equivalent to alveoli. Mutant larvae responded faster to avoid a hypoxic environment (5% oxygen), and ORMDL-expressing adults exposed to cigarette smoke had a reduced lifespan, compared to matched controls. ORMDL-overexpressing flies also had reduced expression of EGFR signaling target genes (ac, spi, cora), consistent with the hypothesis that defective epithelial repair caused by EGFR signaling is linked to asthma development.
[updated May 2019 by FlyBase; FBrf0222196]