B6-RCL-hLPA/Alb-cre/TG(APOB) Mice

Catalog Number: C001553

Genetic Background: C57BL/6NCya

Reproduction: B6-Tg(APOB) x B6-hLPA(CKI) x Alb-Cre

 

Strain Description

Lipoprotein(a) (LP(a)) is considered one of the risk factors for atherosclerosis, coronary heart disease, stroke, and other cardiovascular diseases (CVD) [1]. It is similar in size and lipid content to low-density lipoprotein (LDL) and contains the lipoprotein ApoB-100, but also includes a variable-length lipoprotein(a) (Apo(a)), which is covalently bound to ApoB-100 via a single disulfide bond. LP(a) plays an important role in systemic lipid transport, guiding inflammatory cells into the vascular wall and causing smooth muscle cell proliferation. In addition, it is also involved in wound healing and tissue repair, interacting with components of the vascular wall and extracellular matrix [2]. LP(a) can also cause arterial narrowing by attaching to the arterial wall, accelerating the formation of blood clots, and leading to a series of pathological changes [3]. The plasma concentration of LP(a) is closely related to genetic factors and is mainly regulated by the LPA gene. Therefore, the LPA gene is an important potential target for treating cardiovascular disease. The LPA gene is expressed in humans and non-human primates but not mice. By crossing mice conditional expression of human LPA (LSL-hLPA) with liver-specific Cre expression mice (Alb-Cre) that specifically overexpress the human LPA gene in the liver can be obtained.

ApoB is a protein that plays a central role in lipid metabolism and cardiovascular disease (CVD) and is responsible for transporting cholesterol and other fat molecules to all tissues throughout the body [4]. The accumulation of cholesterol and other lipids can promote the formation of arterial plaques, leading to arterial narrowing and reduced blood flow, increasing the risk of cardiovascular events such as myocardial infarction and stroke [5]. Therefore, high levels of ApoB are a major risk factor for plaque in cardiovascular diseases such as atherosclerosis. ApoB100 is the most abundant subtype of ApoB in humans and the most important subtype of ApoB in cardiovascular disease (CVD) [6]. Mice overexpressing the human APOB gene have significantly elevated LDL cholesterol in serum.

The B6-RCL-hLPA/Alb-cre/TG(APOB) mice express human LP(a) and ApoB, two risk factors for cardiovascular disease. It can be used in the study of hyperlipidemia, stroke, coronary heart disease, familial hypercholesterolemia (FH), and other atherosclerotic cardiovascular diseases (ASCVD). Internal data (not shown) indicates that, compared to the Cyagen strain B6-LPA(CKI)/Alb-Cre&Tg(APOB) mice (Catalog No. C001494), this model exhibits a more stable expression of human LPA protein at different ages. Please choose the model based on the experimental need for continuous stability of human LPA protein expression.

Strain Strategy

This model is obtained by mating B6-Tg(APOB) (Catalog No. C001435) with B6-hLPA(CKI) mice (Catalog No. C001521) and Alb-Cre mice (Catalog No. C001006).

Application

  • Development and evaluation of LP(a) and ApoB targeted drugs;
  • Research on familial hypercholesterolemia (FH);
  • Research on atherosclerotic cardiovascular disease (ASCVD);
  • Research on other cardiovascular diseases (CVD).

 

Validation Data

1. Levels of human Lipoprotein A (LP(a)) 


Figure 1. Detection of human lipoprotein A (LPA) levels in B6-RCL-hLPA/Alb-cre/TG(APOB) mice (nELISA=4, nBlood Biochemistry=5). Both ELISA and blood biochemistry detection results show that male and female B6-RCL-hLPA/Alb-cre/TG(APOB) mice successfully express human LPA protein, with males exhibiting higher LPA protein levels than females. (Data presented as mean±SD).

2. Levels of human Apolipoprotein B (ApoB)


Figure 2. Detection of human ApoB protein levels in B6-RCL-hLPA/Alb-cre/TG(APOB) mice (nELISA=4, nBlood Biochemistry=5). Both ELISA and blood biochemistry detection results show that male and female B6-RCL-hLPA/Alb-cre/TG(APOB) mice successfully express human ApoB protein. (Data presented as mean±SD).

3. Blood Biochemistry


Figure 3. Blood Biochemistry in B6-RCL-hLPA/Alb-cre/TG(APOB) mice (n=5). Blood biochemistry results show that both male and female B6-RCL-hLPA/Alb-cre/TG(APOB) mice have significantly higher LDL-C levels compared to wild-type (WT) mice. Female B6-RCL-hLPA/Alb-cre/TG(APOB) mice have significantly higher HDL-C levels compared to WT mice, while male B6-RCL-hLPA/Alb-cre/TG(APOB) mice show no significant difference in HDL-C levels compared to WT mice. Additionally, there are no significant differences in T-CHO, TG, ALT, and AST levels between B6-RCL-hLPA/Alb-cre/TG(APOB) mice and WT mice. (Data presented as mean±SEM)

*T-CHO: Total cholesterol; TG: Triglycerides; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.

 

References

[1] Kronenberg F. Lipoprotein(a). Handb Exp Pharmacol. 2022;270:201-232.
[2] Brown MS, Goldstein JL. Plasma lipoproteins: teaching old dogmas new tricks. Nature. 1987 Nov 12-18;330(6144):113-4.
[3] Kamstrup PR, Tybjærg-Hansen A, Nordestgaard BG. Lipoprotein(a) and risk of myocardial infarction--genetic epidemiologic evidence of causality. Scand J Clin Lab Invest. 2011 Apr;71(2):87-93.
[4] Glavinovic T, Thanassoulis G, de Graaf J, Couture P, Hegele RA, Sniderman AD. Physiological Bases for the Superiority of Apolipoprotein B Over Low-Density Lipoprotein Cholesterol and Non-High-Density Lipoprotein Cholesterol as a Marker of Cardiovascular Risk. J Am Heart Assoc. 2022 Oct 18;11(20):e025858.
[5] Sniderman AD, Thanassoulis G, Glavinovic T, Navar AM, Pencina M, Catapano A, Ference BA. Apolipoprotein B Particles and Cardiovascular Disease: A Narrative Review. JAMA Cardiol. 2019 Dec 1;4(12):1287-1295.
[6] Behbodikhah J, Ahmed S, Elyasi A, Kasselman LJ, De Leon J, Glass AD, Reiss AB. Apolipoprotein B and Cardiovascular Disease: Biomarker and Potential Therapeutic Target. Metabolites. 2021 Oct 8;11(10):690.