XBP1 and heart failure: We then asked whether the defects observed in AXER-KO medaka, namely, heart failure, could be rescued by the constitutive expression of XBP1(S) or ATF6α(N) from fertilization, namely, at the same time as the loss of AXER in medaka embryo (in other words, from the start of the decrease in the ATP level in the ER lumen), based on our expectation that active XBP1- or ATF6α-mediated induction of gene products would aid the maintenance of the ER protein homeostasis directly.