Analysis of process from ER stress to cell death in an animal model for disease

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Familial neurohypophysial diabetes insipidus (FNDI) model mice were subjected to intermittent water deprivation in order to promote the phenotypes. Electron microscopic analyses demonstrated that, while aggregates are confined to a certain compartment of the ER in the AVP neurons of FNDI mice with water access ad libitum, they were scattered throughout the dilated ER lumen in the FNDI mice subjected to water deprivation for 4 weeks. It is also demonstrated that phagophores, the autophagosome precursors, emerged in the vicinity of aggregates and engulfed the ER containing scattered aggregates. The cytoplasm of AVP neurons in FNDI mice was occupied with vacuoles in the mice subjected to water deprivation for 12 weeks, when 30-40% of AVP neurons are lost. Our data thus demonstrated that autophagy was induced in the AVP neurons subjected to ER stress in FNDI mice.