Animal Models of Cholesterol Gallstone Disease

Abstract

There is no genetically susceptible, spontaneous and naturally occurring animal model for human cholesterol cholelithiasis. The disease has been reported to occur spontaneously only rarely in some primates. The human disease is probably multifactorial; therefore, the finding or development through inbreeding of a spontaneous genetic model is unlikely. The two most popular animals in use today as models are rodent species: hamster and prairie dog. Despite widely different means of dietary induction of the disease in the two, the feature common to both is cholesterol overload. In the case of the essential fatty acid-deficient hamster, the predominant defect is a unique endogenous overproduction through increased total body synthesis of cholesterol. In the prairie dog, the cholesterol overload is simply exogenous due to massive and rapid intestinal absorption. Neither model is remotely physiological. Although a number of useful aspects of the lithogenic process can be studied using these models, certain changes apparently associated with the formation of gallstones under these conditions may in part be a function of the unphysiological dietary requirements for induction of the disease.