A null mutation in murine CD36 reveals an important role in fatty acid andlipoprotein metabolism

A null mutation in the scavenger receptor gene CD36 was created in mice by targeted homologous recombination. These mice produced no detectable CD36 p rotein, were viable, and bred normally. A significant decrease in binding a nd uptake of oxidized low density lipoprotein was observed in peritoneal ma crophages of null mice as compared with those from control mice. CD36 null animals had a significant increase in fasting levels of cholesterol, nonest erified free fatty acids, and triacylglycerol. The increase in cholesterol was mainly within the high density lipoprotein fraction, while the increase in triacylglycerol was within the very low density lipoprotein fraction. N ull animals had lower fasting serum glucose levels when compared with wild type controls. Uptake of H-3-labeled oleate was significantly reduced in ad ipocytes from null mice. However, the decrease was limited to the low ratio s of fatty acid:bovine serum albumin, suggesting that CD36 was necessary fo r the high affinity component of the uptake process. The data provide evide nce for a functional role for CD36 in lipoprotein/fatty acid metabolism tha t was previously underappreciated.