title: Activation of vasopressin neurons leads to phenotype progression in a mouse model for familial neurohypophysial diabetes insipidus.
abstract: Familial neurohypophysial diabetes insipidus (FNDI) is a rare disease that is inherited in an autosomal dominant manner. In a previous study, we made a mouse model for FNDI, which showed progressive polyuria accompanied by inclusion bodies in the arginine vasopressin (AVP) neurons formed by aggregates in the endoplasmic reticulum. The present study was conducted to determine whether the activities of AVP neurons are related to the phenotype progression in the FNDI model. In the first experiment, female heterozygous mice were administered either desmopressin (dDAVP) or a vehicle (control) subcutaneously with osmotic minipumps for 30 days. The dDAVP treatment significantly decreased the urine volume, AVP mRNA expression, and inclusion bodies in the AVP neurons. Urine volume in the dDAVP group remained significantly less than the control for 14 days even after the minipumps were removed. In the second experiment, the males were fed either a 0.2% Na or 2.0% Na diet for 6 mo. Urine AVP excretion was significantly increased in the 2.0% Na group compared with the 0.2% Na group for the first 2 mo but gradually decreased thereafter. Throughout the experiments, urine volume increased progressively in the 2.0% Na group but not in the 0.2% Na group. Immunohistochemical analyses revealed that inclusion bodies in the AVP cells had significantly increased in the 2.0% Na compared with the 0.2% Na group. These data demonstrated that activation of AVP neurons could accelerate the aggregate formation as well as the progression of the polyuria in the FNDI model mice.
authors: Department of Endocrinology and Diabetes, Field of Internal Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Maiko
authors: M
authors: Hiroi
authors: Yoshiaki
authors: Y
authors: Morishita
authors: Masayuki
authors: M
authors: Hayashi
authors: Nobuaki
authors: N
authors: Ozaki
authors: Yoshihisa
authors: Y
authors: Sugimura
authors: Hiroshi
authors: H
authors: Nagasaki
authors: Akira
authors: A
authors: Shiota
authors: Yutaka
authors: Y
authors: Oiso
authors: Hiroshi
authors: H
authors: Arima
mesh_terms: D000818:Animals; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D020790:Diabetes Insipidus, Neurogenic / Q000235:genetics / Q000503:physiopathology*; D018450:Disease Progression; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D006400:Hematocrit; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D009994:Osmolar Concentration; D010641:Phenotype; D010904:Pituitary Gland, Posterior / Q000503:physiopathology*; D012982:Sodium, Dietary / Q000494:pharmacology; D014563:Urodynamics / Q000187:drug effects; D014667:Vasopressins / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D007004:Hypoglycemic Agents; D012982:Sodium, Dietary; D014667:Vasopressins; D003894:Deamino Arginine Vasopressin