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Research Article Free access | 10.1172/JCI4164

Lipoprotein clearance mechanisms in LDL receptor-deficient "Apo-B48-only" and "Apo-B100-only" mice.

M M Véniant, C H Zlot, R L Walzem, V Pierotti, R Driscoll, D Dichek, J Herz, and S G Young

Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141-9100, USA. mveniant@gladstone.ucsf.edu

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Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141-9100, USA. mveniant@gladstone.ucsf.edu

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Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141-9100, USA. mveniant@gladstone.ucsf.edu

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Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141-9100, USA. mveniant@gladstone.ucsf.edu

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Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141-9100, USA. mveniant@gladstone.ucsf.edu

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Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141-9100, USA. mveniant@gladstone.ucsf.edu

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Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141-9100, USA. mveniant@gladstone.ucsf.edu

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Gladstone Institute of Cardiovascular Disease, San Francisco, California 94141-9100, USA. mveniant@gladstone.ucsf.edu

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Published October 15, 1998 - More info

Published in Volume 102, Issue 8 on October 15, 1998
J Clin Invest. 1998;102(8):1559–1568. https://doi.org/10.1172/JCI4164.
© 1998 The American Society for Clinical Investigation
Published October 15, 1998 - Version history
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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.

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