The present invention describes a recombinant rodent model for depression. More particularly, the rodent comprises cells expressing mutations in the WFS1 gene. The rodent is preferably a mouse heterologous for mutations in exon 8 of the WFS1 gene. Preferably, the mutations yield a non-functional wolframin protein that lacks all or some of it transmembrane regions. Methods and compositions for making and using the mouse and cells thereof are disclosed.