Figure 7. Knockdown of GPR146 by AAV-delivered shRNA Lowers Plasma Cholesterol Levels in Mice Lacking LDLR.
(A) Schedule of AAV-mediated knockdown of GPR146 in mice lacking LDLR.
(B and C) Plasma TC levels of male (B) and female (C) mice lacking LDLR before and after injection of AAV8-scramble control or AAV8-Gpr146-shRNA viruses (n=5–6 mice per group, by Student’s t-test).
(D) HDL and VLDL/LDL fractions in plasma of LDLR-deficient mice 6-weeks post AAV injection were separated, and cholesterol levels were measured in both fractions (n=5–6 mice per group, by Student’s t-test).
(E) qPCR expression analysis of cholesterol biosynthetic genes in liver of 6-hour refed male LDLR-deficient mice 6-weeks post AAV injection (n=5–6 mice per group, by Student’s t-test).
(F) Model of the pathway by which depletion of hepatic GPR146 protects against hypercholesterolemia and atherosclerosis.
* p< 0.05, ** p< 0.01; bars in B-D indicate mean± s.d., bars in E indicate mean± s.e.m..
