The present invention relates to compositions and methods for reducing cholesterolemia and its effects. More specifically, the invention is directed, in one embodiment, to methods for screening for compounds that affect
cholesterol levels generally, and in particular, that affect the absorption of
cholesterol. The invention also is directed to methods of screening for compounds that increase
bile acid synthesis. In so doing, the inventors describe useful transgenic cells and animals which lack one or both alleles of the LXRα
gene. Also provided are therapeutic methods designed to reduce
cholesterol levels in suitable subjects. The reduction may be effected by decreasing
cholesterol absorption, increasing
bile acid synthesis, or combinations thereof. Particularly useful in decreasing
cholesterol absorption are RXR agonists, for example, rexinoid compounds. Therapeutic intervention in
cholesterol biosynthesis and diet are additional adjunct therapies. In addition, the present invention relates to candidate compounds that modulate the expression of ABC-1 in a
cell that expresses RXR. Methods of identifying and making a modulator of ABC-1 are disclosed.