Strain specific ANGPTL3 expression analysis in homozygous B-hANGPTL3 mice plus by ELISA. Plasma were collected from wild-type C57BL/6 mice (+/+) and homozygous B-hANGPTL3 mice plus (H/H), and analyzed by ELISA with species-specific ANGPTL3 ELISA kit. Mouse ANGPTL3 was detectable in wild-type mice. Human ANGPTL3 was exclusively detectable in homozygous B-hANGPTL3 mice plus (H/H) but not wild-type mice.

The inhibitory efficiency of the nucleic acid drugs against human ANGPTL3 mRNA in liver tissue in B-hANGPTL3 mice plus. B-hANGPTL3 mice plus were randomly divided into two groups (n=4/group, 10 weeks old). The human ANGPTL3 targeted nucleic acid drugs (synthesized according to patents) and PBS were administered to the mice individually. The nucleic acid drugs was administered in the form of PBS aqueous solution. The drug dosages for all animals were calculated according to the body weight. The mice were sacrificed on day 14, and the liver tissue was collected to detect the expression level of human ANGPTL3 mRNA by qPCR. (A) The schematic diagram of experimental processing. (B) The expression of human ANGPTL3 mRNA in liver after treatment. The inhibition rate in the treatment group was 83.4%. (C) The expression of human ANGPTL3 protein in plasma. The human ANGPTL3 in the treatment group(G2) was significantly reduced compared to the control group(G1), demonstrating that B-hANGPTL3 mice plus provide a powerful preclinical model for in vivo evaluation of human ANGPTL3 targeted nucleic acid drugs. Values are expressed as mean ± SEM.