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(...

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Bibliographic Details
Published in:The Journal of biological chemistry 2000-10, Vol.275 (40), p.31269-31273
Main Authors: Ishigaki, Yasushi, Oikawa, Shinichi, Suzuki, Takashi, Usui, Shinichi, Magoori, Kenta, Kim, Dong-Ho, Suzuki, Hiroyuki, Sasaki, Jun, Sasano, Hironobu, Okazaki, Mitsuyo, Toyota, Takayoshi, Saito, Takao, Yamamoto, Tokuo T.
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Animals
apoE gene
apolipoprotein E
Apolipoproteins E - genetics
Apolipoproteins E - metabolism
Apolipoproteins E - ultrastructure
Chromatography, High Pressure Liquid
Gene Transfer Techniques
hypercholesterolemia
Hypercholesterolemia - genetics
Hypercholesterolemia - metabolism
Kidney Diseases - etiology
Kidney Diseases - genetics
Kidney Diseases - metabolism
Kinetics
lipoprotein glomerulopathy
Male
Mice
Mice, Mutant Strains
Protein Binding
Receptors, LDL - metabolism
Respirovirus - genetics
Sendai virus
Time Factors
Transduction, Genetic
triglycerides
Triglycerides - blood
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M005906200