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J Biol Chem, Vol. 274, Issue 27, 19055-19062, July 2, 1999
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From the A null mutation in the scavenger receptor gene
CD36 was created in mice by targeted homologous recombination. These
mice produced no detectable CD36 protein, were viable, and bred
normally. A significant decrease in binding and uptake of oxidized low
density lipoprotein was observed in peritoneal macrophages of null mice as compared with those from control mice. CD36 null animals had a
significant increase in fasting levels of cholesterol, nonesterified 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. Null animals had lower fasting serum glucose levels when
compared with wild type controls. Uptake of
3H-labeled oleate was significantly reduced in
adipocytes from null mice. However, the decrease was limited to the low
ratios of fatty acid:bovine serum albumin, suggesting that CD36 was
necessary for the high affinity component of the uptake process. The
data provide evidence for a functional role for CD36 in
lipoprotein/fatty acid metabolism that was previously underappreciated.
Division of Hematology/Oncology, Center for Vascular Biology and Departments of
Pathology and Biochemistry, Weill Medical College of Cornell
University, New York, New York 10021 and the
¶ Department of Physiology and Biophysics, State
University of New York at Stony Brook,
Stony Brook, New York 11794-8662
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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