Virus-mediated transduction of apolipoprotein E (ApoE)-sendai develops lipoprotein glomerulopathy in ApoE-deficient mice.
Lipoprotein glomerulopathy (LPG) is a unique renal disease characterized by thrombus-like substances in markedly dilated glomerular capillaries, dysbetalipoproteinemia, and elevated plasma concentrations of apoE. Recent studies identified several apoE mutations in patients with LPG, including apoE2(R145P) Sendai (apoE-Sendai). Virus-mediated transduction of apoE-Sendai in apoE-deficient hypercholesterolemic mice resulted in insufficient correction of hypercholesterolemia and a marked and temporal induction of plasma triglyceride levels. In vitro binding studies showed that apoE-Sendai has a reduced affinity for the low density lipoprotein receptor, suggesting that dysbetalipoproteinemia in LPG is caused by the apoE mutation. Furthermore, histological examination revealed marked intraglomerular depositions of apoE-containing lipoproteins in mice injected with apoE-Sendai virus. These LPG-like depositions were detected 6 days after virus injection and were sustained for at least 60 days. Our results demonstrated that apoE-Sendai is an etiological cause of LPG.
Ishigaki
Y
Y
Tohoku University Gene Research Center, Sendai 981-8555, Japan.
Oikawa
S
S
Suzuki
T
T
Usui
S
S
Magoori
K
K
Kim
D H
DH
Suzuki
H
H
Sasaki
J
J
Sasano
H
H
Okazaki
M
M
Toyota
T
T
Saito
T
T
Yamamoto
T T
TT
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure; D002851:Chromatography, High Pressure Liquid; D018014:Gene Transfer Techniques; D006937:Hypercholesterolemia / Q000235:genetics / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011485:Protein Binding; D011973:Receptors, LDL / Q000378:metabolism; D018108:Respirovirus / Q000235:genetics*; D013997:Time Factors; D014161:Transduction, Genetic; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D011973:Receptors, LDL; D014280:Triglycerides