Different susceptibilities to the formation of cholesterol gallstones in mice.

In the search for an animal model of genetic determinants of cholesterol cholelithiasis, we found strain, gender and individual differences in mice. Male black (C57BL6J) mice had a 50% incidence of cholesterol gallstones after they consumed lithogenic food similar to that used by Tepperman et al. for 2 weeks, whereas similarly treated male agouti (CBA/J) mice and females of both strains were free of gallstones. The male and female mice of both strains were fertile at 8 weeks of age, and the male black mice were first susceptible to induction of gallstones at 24 weeks of age. Male agouti mice of the same age did not form gallstones until they had consumed the lithogenic food for 8 weeks. The gallbladder biles of both strains were supersaturated with cholesterol during the lithogenic regimen. The male agouti mice had much higher fractional turnover rates of [24-14C]cholic acid than did the male black mice. In spite of their small total cholate pools, the agouti mice had higher rates of new cholate synthesis than did the black mice. The rate of disappearance of [1,2-3H]cholesterol from the blood was higher in the male agouti than in the black mice. The gallbladders of the agouti mice contained less bile and weighed less empty than gallbladders of the black mice. They also did not increase in volume in response to the lithogenic diet as much as gallbladders of the black mice. The difference in gallstone induction times between male and female black mice was as great as the difference between the two strains.(ABSTRACT TRUNCATED AT 250 WORDS)