Induction of gallstones in mice by feeding a cholesterol-cholic acid containing diet

Abstract

A high incidence of gallstones (90%) was observed during a study of the effect on the serum cholesterol of feeding an "atherogenic" diet to aurothioglucose- (ATG) injected obese and nonobese mice. In a second experiment (without ATG) groups of eight male and eight female mice were examined at monthly intervals after having been started on the stone-inducing diet. Gallstones began to appear after 2 months and the incidence increased to 75% after 8 months. Although there was no significant sex difference in cumulative incidence, stones tended to appear earlier in females. Serum cholesterol values were, however, significantly higher in males during most of the experiment. In a third experiment the following features of the original treatment were singly and systematically excluded from the regimens of groups of 20 male mice: 0.04% thiouracil in drinking water, high fat (30%), cholesterol (1%), cholic acid (0.5%), and low protein (11%). It was found that the combination of cholesterol and cholic acid was necessary and sufficient for stone formation if food intake remained adequate and liver function was unimpaired.