Figure 4. Sortilin expression promotes LDL uptake and lysosomal catabolism in vivo.

(A–D) Control mice and mice receiving AAVs encoding wild-type or mutant Sort1 were injected with 2 × 10⁶ counts of ¹²⁵I-LDL via tail vein. Blood was drawn serially 2 minutes and 1, 3, 6, 9, and 24 hours after injection. All counts were normalized to the 2-minute count. Clearance curves (A) and FCRs (B) demonstrated a dose-dependent increase in LDL clearance in wild-type mice expressing Sort1. Clearance curves (C) and FCRs (D) demonstrated that wild-type sortilin and Sort.LAYA increased LDL clearance, while Sort.Stop did not increase plasma LDL clearance (E and F) Clearance and FCRs demonstrating a 40% reduction in FCR in Sort1^–/– mice compared with wild-type mice and a 50% reduction in FCR in Ldlr^–/–;Sort1^–/– mice compared with Ldlr^–/– mice.