TG-hAPOC3 Mice

Catalog Number: C001588

Strain Name: C57BL/6NCya-Tg(hAPOC3)/Cya

Genetic Background: C57BL/6NCya

Reproduction: Carrier x WT

 

Strain Description

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.

Strain Strategy

The human APOC3 gene sequence, including the 5'UTR and 3'UTR sequences, was integrated into the mouse genome using transgenic (TG) technology.


Application

  • Development, screening, and preclinical efficacy evaluation of therapeutics targeting human APOC3;
  • Investigation of the pathogenic mechanisms and therapeutic strategies for hypertriglyceridemia (HTG).

 

Validation Data

1. ELISA Assay


Figure 1. The expression of human APOC3 protein in plasma from 8-week-old male TG-hAPOC3 and wild-type (WT) mice. ELISA results demonstrate significant expression of human APOC3 protein in the plasma of TG-hAPOC3 males (Bars represent mean ± SEM, n=3).

 

2. Blood Biochemistry Analysis


Figure 2. Plasma Blood Biochemistry Analysis of 6-week-old TG-hAPOC3 Mice and Wild-Type (WT) Mice. The data reveal no significant differences in plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) between TG-hAPOC3 and WT mice. Plasma triglyceride (TG) levels were significantly higher in male TG-hAPOC3 mice compared to male WT mice and slightly elevated in female TG-hAPOC3 mice compared to female WT mice, but the difference was not statistically significant (Bars represent mean ± SEM, n=5).



References
[1]Borén J, Packard CJ, Taskinen MR. The Roles of ApoC-III on the Metabolism of Triglyceride-Rich Lipoproteins in Humans. Front Endocrinol (Lausanne). 2020 Jul 28;11:474.
[2]Ramms B, Gordts PLSM. Apolipoprotein C-III in triglyceride-rich lipoprotein metabolism. Curr Opin Lipidol. 2018 Jun;29(3):171-179.
[3]Chebli J, Larouche M, Gaudet D. APOC3 siRNA and ASO therapy for dyslipidemia. Curr Opin Endocrinol Diabetes Obes. 2024 Apr 1;31(2):70-77.