TY - JOUR
T1 - Lipoprotein clearance mechanisms in LDL receptor-deficient 'apo-B48- only' and 'apo-B100-only' mice
AU - Véniant, Murielle M.
AU - Zlot, Constance H.
AU - Walzem, Rosemary L.
AU - Pierotti, Vincenzo
AU - Driscoll, Robert
AU - Dichek, David
AU - Herz, Joachim
AU - Young, Stephen G.
PY - 1998/10/15
Y1 - 1998/10/15
N2 - 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.
AB - 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.
KW - Adenovirus-mediated gene transfer
KW - LDL receptor deficiency
KW - LDL receptor-related protein
KW - Low density lipoproteins
KW - Mouse apo-B radioimmunoassay
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U2 - 10.1172/JCI4164
DO - 10.1172/JCI4164
M3 - Article
C2 - 9788969
AN - SCOPUS:0032532670
SN - 0021-9738
VL - 102
SP - 1559
EP - 1568
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 8
ER -