Lipoprotein clearance mechanisms in LDL receptor-deficient "Apo-B48-only" and "Apo-B100-only" mice.
Open Access
- 15 October 1998
- journal article
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 102 (8) , 1559-1568
- https://doi.org/10.1172/jci4164
Abstract
The role of the low density lipoprotein receptor (LDLR) in the clearance of apo-B48-containing lipoproteins and the role of the LDLR-related protein (LRP) in the removal of apo-B100-containing lipoproteins have not been clearly defined. To address these issues, we characterized LDLR-deficient mice homozygous for an "apo-B48-only" allele, an "apo-B100-only" allele, or a wild-type apo-B allele (Ldlr-/- Apob48/48, Ldlr-/-Apob100/100, and Ldlr-/-Apob+/+, respectively). The plasma apo-B48 and LDL cholesterol levels were higher in Ldlr-/-Apob48/48 mice than in Apob48/48 mice, indicating that the LDL receptor plays a significant role in the removal of apo-B48-containing lipoproteins. To examine the role of the LRP in the clearance of apo-B100-containing lipoproteins, we blocked hepatic LRP function in Ldlr-/-Apob100/100 mice by adenoviral-mediated expression of the receptor-associated protein (RAP). RAP expression did not change apo-B100 levels in Ldlr-/-Apob100/100 mice. In contrast, RAP expression caused a striking increase in plasma apo-B48 levels in Apob48/48 and Ldlr-/-Apob48/48 mice. These data imply that LRP is important for the clearance of apo-B48-containing lipoproteins but plays no significant role in the clearance of apo-B100-containing lipoproteins.Keywords
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