Both deletion of IRE1α (Urano et al., 2000; Zhang et al., 2005) and of XBP1 (Reimold et al., 2000) cause embryonic lethality, but XBP1 KO mice are rescued with an XBP1 transgene specifically expressed in the liver (Lee et al., 2005), while IRE1α KO mice are rescued when the placenta expresses IRE1α (Iwawaki et al., 2009), and the resulting rescued mice display relatively mild symptoms, that ishyperglycemia, hypoinsulinemia, and decreased antibody titers, despite the lack of IRE1α (Iwawaki et al., 2010). Here, ERN1 is linked to Hypoinsulinemia.