Pathogenesis and genetics of the polydipsia-polyuria defect in the SWV strain of house mice

In the SWV strain of mice, old females have a severe increase in water intake and urine output. This polydipsia-polyuria defect was investigated. The SWV females' urine was hypotonic, contained no glucose or blood, and had no increase in protein or pH. The defect thus appeared to be some form of diabetes insipidus. The mice were then tested for their response to water deprivation, saline ingestion, and exogenous vasopressin (pitressin tannate). The results indicated that the defect was nephrogenic diabetes insipidus. Histological studies showed that there was an adequate amount of neurosecretory material in the posterior pituitaries and that the adrenals were normal. At 4 months of age, the SWV females' kidneys were normal, but from 6 months of age the kidneys were progressively abnormal until by 17 months the kidneys had severely degenerated. At 12 months of age the females' kidneys were abnormally large, hydronephrotic, and had severely dilated and hyperplastic tubules in the cortico-medullary zone. Some of the dilated tubules contained eosinophilic casts and there was some focal interstitial nephritis. At 17 months, the females' kidneys had severe interstitial nephritis and some fibrosis around the tubules, and some hyalinization in the cortex. The females also had a progressive anaemia but preliminary studies indicated no large increase in blood urea nitrogen. Thus the SWV females had a nephrogenic diabetes insipidus which first appeared at 4 to 6 months of age. While the defect resembled human nephro-nophthisis and hypokalemia in some symptoms, it did appear to be unique. Amyloid kidneys, polycystic kidneys, and diabetes mellitus have been ruled out as the cause of the defect but hypokalemia and hypercalcemia are still possibilities. The SWV males had a milder expression of the defect and did not show the polydipsia until 7 to 8 months of age. They had a milder form of the polydipsia, the concentrating defect, and the anaemia, but showed no kidney abnormalities. The defect was sex influenced possibly due to the difference in steroid hormones. Polydipsic SWV mice were crossed to control C3H mice and F₁, F₂, BC[sub SWV], and BC[sub C3H] progeny in each generation indicated that one or two dominant genes determined the polydipsic defect in the SWV strain. There was no sex linkage. A quantitative analysis of mean water intakes for each generation indicated that non-genetic factors influenced the polydipsia multiplicatively. Some of these non-genetic factors were sex, age, body weight, type of feed ration, and parity.Medicine, Faculty ofMedical Genetics, Department ofGraduat