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, dysbe talipoproteinemia, and elevated plasma concentrations of apoE, Recent studi es 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 correctio n of hypercholesterolemia and a marked and temporal induction of plasma tri glyceride levels. In vitro binding studies showed that apoE-Sendai has a re duced affinity for the low density lipoprotein receptor, suggesting that dy sbetalipoproteinemia in LPG is caused by the apoE mutation. Furthermore, hi stological 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 sustai ned for at least 60 days. Our results demonstrated that apoE-Sendai is an e tiological cause of LPG.