Deficiency of low density lipoprotein receptors in liver and adrenal gland of the WHHL rabbit an animal model of familial hypercholesterolemia.

摘要

The WHHL (Watanabe heritable hyperlipidemic) rabbit has been proposed as an animal model for human familial hypercholesterolemia. Homozygous WHHL rabbits have marked increases in the plasma level of low density lipoprotein (LDL), removal of LDL from their plasma is delayed, and LDL receptors are absent from their cultured fibroblasts [Tanzawa, K., Shimada, Y., Kuroda, M., Tsujita, Y., Arai, M. & Watanabe, Y. (1980) FEBS Lett. 118, 81--84]. We here report that membranes from the liver and adrenal gland of WHHL rabbits lack high-affinity LDL receptors. In normal rabbit membranes, binding of LDL to this receptor required calcium and is inhibited by EDTA. The LDL receptor binds rabbit 125I-labeled beta-migrating very low density lipoprotein (beta-VLDL), which contains apoproteins B and E, as well as rabbit 125I-labeled LDL, which contains only apoprotein B. It does not bind high density lipoprotein or methyl-LDL. All of these properties are identical with those of the LDL receptor of cultured fibroblasts. We conclude that a deficiency of hepatic and adrenal LDL receptors contributes to the hypercholesterolemia of the WHHL rabbits.