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.
A genetically susceptible, spontaneous and naturally occurring animal model for human cholesterol gallstone disease is yet to be identified. A frequent, spontaneous incidence of cholesterol gallstone disease does not occur naturally in any genetically predisposed animal species. Discovery or creation of cholelithiasis in a convenient animal species by inbreeding, i.e., the low density lipoprotein (LDL) (receptor-deficient) hereditable hyperlipidemia (Watanabe) rabbits as a surrogate for human familial hypercholesterolemia, would thus constitute a major scientific advance (1). From a genetic standpoint, however, the human disease does not appear to represent the result of a single defect. Instead, available evidence suggests the presence of a pathophysiological mosaic consisting of a number of interacting risk factors peculiar to man such as biliary cholesterol supersaturation, an abnormality of biliary proteins, relative gallbladder stasis and other unidentified potential defects. For this reason, in all of the wide variety of animal models proposed for this disease, one or more distinctly unphysiologic perturbations has been necessarily imposed to induce the disease process. Thus, all of the existing animal models in use may be considered to have comparative strengths and shortcomings even when focused to specific purposes. This paper will concentrate on the limited number of currently popular models employed in studies of the disease.