Pregnancy dependence of mammary tumours in DDD mice congenic for Mtv-2, DDD/1-Mtv-2/Mtv-2

Mammary tumours developed in 110 (95.7%) of 115 DDD/1- Mtv-2/Mtv-2 (DDD/1- Mtv-2) and 24 (47·1%) of 51 DDD/1fDDD/1- Mtv-2 (DDD/1f Mtv-2) force-bred female mice during a one-year period. The mean tumour age±SE was 220±7 and 269±7 days, respectively. These tumours were examined for responsiveness to pregnancies by comparing their growth after transplantation between virgin and breeding recipients. Of 73 tumours from DDD/1- Mtv-2 mice, 9 (12%) were completely pregnancy-dependent (CPD), 3 (4%) pregnancy-dependent (PD), 9 (12%) pregnancy-responsive (PR), and 52 (71%) pregnancy-independent (PD), and of 25 tumours from DDD/1f Mtv-2 mice, one (4%) was CPD, one (4%) PR, and 23 (92%) PI. Although most tumours were heterogeneous in morphology and there was no clear relation between morphology and PO properties, most CPD tumours were type P and considered to be connected with mammary plaques. When 9 CPD tumours from DDD/1- Mtv-2 mice were serially transplanted in breeders, 6, 2 and one progressed to lose pregnancy dependence within 3, 8 and 18 generations, respectively. DDD/1- Mtv-2 mice will provide a model for studies on progression of mammary tumours from hormone-dependent to autonomous states.

Influence of chronic oestrogen treatment on severity of hydronephrosis in inbred DDD mice

It has been reported that mice treated chronically with oestrogen (oestradiol propionate) increase their bladder urine volume. Since inbred DDD mice, particularly male DDD mice, lack a protective mechanism against vesicoureteral reflux (VUR), chronic oestrogen treatment may increase the pressure in the renal pelvis and lead to severe hydronephrosis. The present studies were carried out to confirm this hypothesis. Results of a least-squares analysis of variance showed that the severity of hydronephrosis was more severe after treatment with high doses of oestrogen (1·0 and 5·0 mg/kg/week) in entire and castrated male DDD mice. Hydroureter was also observed in the same groups. Intra-vesicular pressure was 7 to 12 cmH2O higher in mice of these groups than in control DDD mice. High doses of oestrogen had no effect on the kidneys of C57BL/6 mice which showed normal protection against VUR, though it increased bladder urine volume. These findings support the hypothesis that hydronephrosis in DDD mice is caused by an incomplete protective mechanism against VUR.

Inheritance of hydronephrosis in the inbred mouse strain DDD

The mode of inheritance of hydronephrosis was investigated by crossing inbred DDD mice having a high incidence of hydronephrosis and C57BL/6 mice having normal kidneys. In the males, incidences of hydronephrosis in F1 animals were intermediate between the two parental strains at a rate of 32·6% in (DDD × C57BL/6)F1 and 23·4% in reciprocal F1. The same tendency was observed in F2 male animals. In BCF1 males, the number of affected mice was higher in (C57BL/6 × DDD) F1 × DDD (72·4%) than in (DDD × C57BL/6)F1 × C57BL/6 (11·1%). A few affected mice were found among the females of hybrids F1, F2 and BCF1. These results suggested that hydronephrosis in the DOD strain of mice was controlled by polygenes, and that male hormones may have some effect on the occurrence of hydronephrosis.

Hydronephrosis in the inbred mouse strain DDD

The inbred mouse strain DDD was found to have an extremely high incidence of hydronephrosis (37/37 in adult males and 12/32 in adult females). The hydronephrosis was classified as open with no definite cause for obstruction. The condition was either unilateral in the right kidney or bilateral. Another feature of the hydronephrosis kidney was circulatory failure. Hydronephrosis in strain DDD mice is considered to be a useful experimental animal model with additional possible use, in investigating disturbances of renal haemo-dynamics and function.