Basic Information
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Gene targeting strategy
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Gene targeting strategy for B-hANGPTL3 mice plus. The genome of mouse Angptl3 gene including 5’UTR and 3’UTR was replaced by human ANGPTL3 genome including 5’UTR and 3’UTR in B-hANGPTL3 mice plus.
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Protein expression analysis
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Species-specific ANGPTL3 protein expression analysis in wild-type and humanized B-hANGPTL3 mice plus. Plasma was collected from wild-type C57BL/6 (+/+) and homozygous B-hANGPTL3 (H/H) mice plus and analyzed by ELISA using species-specific ANGPTL3 kits. Mouse ANGPTL3 was detected in wild-type mice, while human ANGPTL3 was detected in B-hANGPTL3 mice plus.
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Inhibitory efficiency of the nucleic acid drugs against the ANGPTL3 mRNA expression level
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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%, 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.
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Summary
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Protein expression analysis:
Human ANGPTL3 was exclusively detectable in homozygous B-hANGPTL3 mice plus (H/H) but not in wild-type mice (+/+), and mouse ANGPTL3 was detectable in wild-type mice (+/+).
In vivo efficacy:
Human ANGPTL3 targeted nucleic acid drugs (synthesized according to patents) was efficacious in B-hANGPTL3 mice plus.
