Analysis of the vasopressin system and water regulation in genetically polydipsic mice

Polydipsic mice, STR/N, which show extreme polydipsia and polyuria, were di scovered in 1958. In the STR/N, urine outputs are much higher than in contr ol mice. The possibility of an abnormal regulation of the arginine vasopres sin (AVP) system, or an abnormality in the renal susceptibility to AVP, sho uld be considered. In this study me investigated the AVP system and water r egulation in STR/N. We sequenced the AVP and the AVP V-2-receptor genes of the STR/N by direct sequencing. No mutation was found in either of them. AV P gene expression examined by in situ hybridization and plasma sodium in 8- wk-old STR/N was significantly lower than in control mice, whereas it was s ignificantly higher at 20 wk. Renal sensitivity to injected AVP was attenua ted in 20-wk-old STR/N. The suppression of AVP synthesis due to excessive w ater retention in 8-wk-old STR/N suggests that polydipsia may be the primar y cause in this strain. The 20-wk-old STR/N became dehydrated with the acce leration of AVP synthesis, which might have resulted from secondary desensi tization to AVP.