Figure 6. ER retention of hLDLR^G544V, but not hPCSK9^Q152H, causes a robust UPR activation in liver.

(A and B) The livers of Pcsk9^–/– mice (n = 5) treated with AAV encoding EV, hPCSK9^WT, and ER-retained variants hPCSK9^Q152H and hLDLR^G544V were examined for expression of UPR markers p-PERK, IRE1α, sXBP1, p-eIF2α, ATF4, and CHOP by immunoblotting and real-time PCR. (C) Hepatic p-PERK and p-IRE1α expression was also examined via IHC staining. Staining intensity was quantified using ImageJ software. (D) Liver injury was examined in these mice via quantification of serum ALT activity. Values are expressed as mean ± SD. *P < 0.05. ANOVA was used for all statistical comparisons (A–D). Scale bars: C, 200 μm.