USING GENETICALLY-ENGINEERED MICE TO UNDERSTAND APOLIPOPROTEIN-B DEFICIENCY SYNDROMES IN HUMANS

Several human diseases are characterized by defects in the synthesis a nd secretion of the apolipoprotein (apo) B-containing lipoproteins. Fa milial hypobetalipoproteinemia is caused by mutations in the apo-B gen e and is characterized by abnormally low plasma concentrations of apo- B and low-density lipoprotein (LDL) cholesterol. Another apo-B deficie ncy syndrome, abetalipoproteinemia, is caused by mutations in the gene for microsomal triglyceride transfer protein (MTP). MTP is a microsom al protein that is thought to transfer lipids to the apo-B protein as it is translated, allowing it to attain the proper conformation for Li poprotein assembly. A third apo-B deficiency syndrome, Anderson's dise ase (or chylomicron retention disease), is characterized by the inabil ity to secrete apo-B-containing chylomicrons from the intestine but an apparently normal capacity to secrete Lipoproteins from the liver. To more fully understand these human apo-B deficiency syndromes, our lab oratory has generated and characterized gene-targeted mouse models. Th is review summarizes what has been learned from these animal models.