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. |