(M1030-04-21) Overexpression of Human ApoC3 in Mice Leads to Hypertriglyceridemia and Induces Key CVD-related Lipid Biomarkers

Purpose: ApoC3 increases plasma triglyceride (TG) and causes hypertriglyceridemia. Elevated triglyceride is one of the key contributors of cardiovascular and metabolic diseases. A strong correlation of apoC3 and plasma TG level was demonstrated using a mouse transgenic model, B6;CBA-Tg(APOC3)3707Bres/J, that overexpresses human apoC3 in liver and small intestine. To better understand this model, we investigated the link between apoC3 and major cardiovascular diseases related metabolic risk biomarkers.

Methods: Twenty nine female and 24 male B6;CBA-Tg(APOC3)3707Bres/J mice at age between 13 and 15 weeks were recruited in this study. The plasma concentrations of human apoC3 were measured by MSD, an electrochemiluminescence based immunoassay. The concentrations of total cholesterol (TC), triglyceride (TG), LDL and HDL were analyzed by Roche Cobas C311 analyzer.

Results: A wide range of plasma apoC3 protein from 5.1 to 41 mg/mL was seen in this cohort and significantly higher level in male vs. female (27.5 +/- 0.013 vs. 10.0 +/- 0.005 mg/mL) was also observed. Compare with wild type mouse strains (e.g. C57BL/6), B6;CBA-Tg(APOC3)3707Bres/J have remarkably higher levels of TG, TC, LDL and lower level of HDL. Although the increase of LDL is notable, the major contribution of the TC increasing was not from LDL and HDL. (Table 1). In addition, plasma human apoC3 protein level of individual subject was positively correlated with the plasma TG (R²=0.46, P< 0.01) and TC (R²=0.52, P< 0.01). In consistent with the gender difference on lipid profile, a stronger correlation of human apoC3 with TC in female group (R²=0.86, P< 0.01) was demonstrated. Furthermore, a correlation between TC and TG (R²=0.70, P< 0.01) was revealed.

Conclusion: Over-expression of human apoC3 in B6;CBA-Tg(APOC3)3707Bres/J mice not only leads to hypertriglyceridemia, but also induced key CVD-related lipid biomarkers in hypercholesterolemia and elevated LDL-C. Compare with other mouse models, the unique lipid profile with high TG/TC, LDL-C/HDL ratio, would make B6;CBA-Tg(APOC3)3707Bres/J be a more suitable model for human hypertriglyceridemia / dyslipidemia research.

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Acknowledgements: The study was performed at WuXi AppTec/Xenobiotic Laboratories, Inc. and adhered to the approved study protocol, protocol amendment(s) if any, and related standard operating procedures (SOP). Animal related work was reviewed and approved by WuXi AppTec’s Institutional Animal Care and Use Committee (IACUC) according to the Guide for the Care and Use of Laboratory Animals.


Table 1. Tg(APOC3)3707Bres mouse has unique lipid profile with high TG/TC, LDL-C/HDL ratio compare with other mouse strains and would be a more suitable model for human hypertriglyceridemia / dyslipidemia research.


Plasma human apoC3 protein level of individual subject was positively correlated with the plasma TG (R2=0.46, P<0.01) and TC (R2=0.52, P<0.01).


Stronger correlation of human apoC3 with TC observed in female group (R2=0.86, P<0.01).