Polycystic kidney and liver disease and corticosterone changes in the cpk mouse.

Mice homozygous for the mutation cpk develop a lethal infantile polycystic kidney disease (PKD) and have abnormal elevations of corticosterone in the postnatal period. We examined the development of these elevated glucocorticoid levels in early life. The histological progression of a cystic lesion of the biliary ducts in older heterozygotes was also studied. Normal mice had low (less than 85 nmol/liter) or undetectable (less than 36 nmol/liter) levels from the sixth to twelfth day of life. Corticosterone levels were significantly higher in all homozygote (cpk/cpk) and some of the normal sibs, who were presumed to be heterozygote (cpk/+) mice compared to age-matched controls from day seven to 12. Corticosterone levels were similar from the fifteenth day. A significant proportion of adult obligate heterozygotes from breeding pairs were found to have focal areas of cystic dilatation of the biliary ducts, in the absence of any renal abnormality. The incidence of this lesion increased with age (10% at 150 days, 23% at 300 days, 29% at 450 days, 65% at greater than 450 days of age). The livers of homozygote mice dying in infancy, and control adult mice of the C57BL/6J background strain were free of cysts. The finding of hepatic cysts is reminiscent of adult type PKD. The cpk model thus supports the concept that the different forms of PKD may represent varying expression of a similar gene complex.