Lipoprotein clearance mechanisms in LDL receptor-deficient 'apo-B48- only' and 'apo-B100-only' mice

Murielle M. Véniant, Constance H. Zlot, Rosemary L. Walzem, Vincenzo Pierotti, Robert Driscoll, David Dichek, Joachim Herz, Stephen G. Young

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113 Scopus citations

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(-/-) Apob(48/48), Ldlr(-/-)Apob(100/100), and Ldlr(-/-)Apob(+/+), respectively). The plasma apo-B48 and LDL cholesterol levels were higher in Ldlr(-/-)Apob(48/48) mice than in Apob(48/48) 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(-/-)Apob(100/100) mice by adenoviral-mediated expression of the receptor-associated protein (RAP). RAP expression did not change apo- B100 levels in Ldlr(-/-)Apob(100/100) mice. In contrast, RAP expression caused a striking increase in plasma apo-B48 levels in Apob(48/48) and Ldlr(- /-)Apob(48/48) 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.

Original languageEnglish (US)
Pages (from-to)1559-1568
Number of pages10
JournalJournal of Clinical Investigation
Volume102
Issue number8
DOIs
StatePublished - Oct 15 1998

Keywords

  • Adenovirus-mediated gene transfer
  • LDL receptor deficiency
  • LDL receptor-related protein
  • Low density lipoproteins
  • Mouse apo-B radioimmunoassay

ASJC Scopus subject areas

  • Medicine(all)

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    Véniant, M. M., Zlot, C. H., Walzem, R. L., Pierotti, V., Driscoll, R., Dichek, D., Herz, J., & Young, S. G. (1998). Lipoprotein clearance mechanisms in LDL receptor-deficient 'apo-B48- only' and 'apo-B100-only' mice. Journal of Clinical Investigation, 102(8), 1559-1568. https://doi.org/10.1172/JCI4164