Although the carriers are normal at birth, polyuria and polydipsia appear several months or years later. Previously, we made mice possessing a mutation causing FNDI and reported that the mice manifested progressive polyuria as do the patients with FNDI. Here, we report that decreases in AVP mRNA expression in the supraoptic nucleus were accompanied by shortening of the AVP mRNA poly(A) tail length in the FNDI mice, a case in which aggregates accumulated in the endoplasmic reticulum (ER) of the hypothalamic AVP neurons.
Expression levels of AVP heteronuclear RNA in the supraoptic nucleus, a sensitive indicator for gene transcription, were not significantly different between FNDI and wild-type mice.
Incubation of hypothalamic explants of wild-type mice with ER stressors (thapsigargin and tunicamycin) caused shortening of the poly(A) tail length of AVP and oxytocin mRNA, accompanied by decreases in their expression.
On the other hand, an ER stress-reducing molecule (tauroursodeoxycholate) increased the poly(A) tail length as well as the expression levels of AVP and oxytocin mRNA. These data reveal a novel mechanism by which ER stress decreases poly(A) tail length of neurohypophysial hormones, probably to reduce the load of unfolded proteins.