TG-hAPOC3 Mouse

Apolipoprotein C-III (ApoC-III), encoded by the APOC3 gene, is a 79-amino acid glycoprotein primarily synthesized in the liver, with minor production in the intestine. ApoC-III is a key component of triglyceride-rich lipoproteins (TRLs), including chylomicrons and very low-density lipoprotein (VLDL). Its primary functions include inhibiting lipoprotein lipase (LPL)-mediated hydrolysis of triglycerides within TRLs and modulating hepatic uptake of TRL remnants, thereby elevating plasma triglyceride levels. Consequently, ApoC-III is crucial in regulating plasma triglyceride levels ^[1-2]. Elevated APOC3 expression leads to increased ApoC-III levels, which is associated with hypertriglyceridemia (a risk factor for cardiovascular disease) and conditions such as familial hypertriglyceridemia, metabolic syndrome, and type 2 diabetes. Therefore, targeting the reduction of APOC3 expression or blocking its protein function offers a therapeutic avenue for hypertriglyceridemia and mitigating cardiovascular disease risk ^[3].

The TG-hAPOC3 mouse is a humanized model generated by integrating the human APOC3 gene sequence, encompassing the upstream and downstream untranslated regions (UTRs), into the mouse genome, enabling the expression of human ApoC-III protein in vivo. This model is valuable for developing therapeutics targeting human APOC3, such as small interfering RNA (siRNA) and antisense oligonucleotides (ASOs), for the treatment of hypertriglyceridemia.