ERN1 and diabetes mellitus: IRE1α-deficient mice have defects in placental angiogenesis, and they display abnormal liver development, reaching lethality after about 11–12 days of gestation.13, 37 Furthermore, IRE1α-conditional KO mice have been reported to exhibit pathological features of various diseases, such as diabetes or hepatosteatosis.14, 23, 27, 38 IRE1β-deficient mice grow and reproduce normally under normal rearing conditions, but their pathological phenotype is more severe than that of wild-type mice under conditions of intestinal inflammation.3