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

First Author  Véniant MM Year  1998
Journal  J Clin Invest Volume  102
Issue  8 Pages  1559-68
PubMed ID  9788969 Mgi Jnum  J:51022
Mgi Id  MGI:1313233 Doi  10.1172/JCI4164
Citation  Veniant MM, et al. (1998) Lipoprotein clearance mechanisms in LDL receptor-deficient Apo-B48-only and Apo-B100-only mice. J Clin Invest 102(8):1559-68
abstractText  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.
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