B6J-Apoe KO Mice

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Catalog Number: C001507

Strain Name: C57BL/6JCya-Apoeem1/Cya

Genetic Background: C57BL/6JCya

Reproduction: Homozygote × Homozygote


Strain Description

Apolipoprotein E (ApoE) is a lipid particle-associated polymorphic carrier protein encoded by the APOE gene. It is a core component of plasma lipoproteins, participating in the production, transport, and clearance of lipoproteins. ApoE is associated with chylomicrons, chylomicron remnants, high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and intermediate-density lipoprotein (IDL), especially showing preferential binding to HDL [1]. ApoE is the most important lipid transport protein in the body, having a profound impact on lipid metabolism. The interaction of ApoE with the low-density lipoprotein receptor (LDLR) is essential for the normal processing (catabolism) of triglyceride-rich lipoproteins [2]. In peripheral tissues, ApoE is primarily produced by the liver and macrophages and mediates cholesterol metabolism. In the central nervous system, ApoE is primarily produced by astrocytes and is the major cholesterol carrier in the brain. ApoE is essential for the transport of cholesterol from astrocytes to neurons [1-4]. In addition, ApoE forms a complex with activated C1q, becoming a checkpoint inhibitor target of the classical complement pathway [5]. Polymorphisms of the APOE are associated with Alzheimer's disease and lipid accumulation, hyperlipidemia, atherosclerosis, high cholesterolemia, etc., and are related to the risk of various cardiovascular diseases.

The B6J-Apoe KO mouse is a model of ApoE deficiency. It was generated by gene editing technology to knock out the Apoe gene in mice. ApoE protein synthesis is blocked in these mice, leading to elevated cholesterol levels and spontaneous atherosclerosis. Cholesterol levels and atherosclerosis in mice fed a high-fat diet (HFD) are further exacerbated. The B6J-Apoe KO mice are viable and can be used for research in the fields of hypercholesterolemia, atherosclerosis, and Alzheimer's disease.

 

The target sequence of this strain was designed to include exons 2-4 of the mouse Apoe gene.

● Cardiovascular disease research: Hypercholesterolemia, hyperlipidemia, atherosclerosis, etc.;

● Body metabolism mechanism research: Fat and cholesterol metabolism;

● Neurodegenerative disease research: Alzheimer's disease.

1. Growth Curves

Figure 1. Body weight trajectories of B6J-Apoe KO and wild-type (WT) mice on normal diet (ND) and high-fat diet (HFD) conditions. Results showed that B6J-Apoe KO mice grew at a similar rate in normal and HFD conditions. WT mice fed HFD gained weight, and internal inspection data showed that at 20 weeks, the aortic arch and aortic vessels in WT mice were normal and no atherosclerotic plaque was formed.*
*High-fat diet was purchased from Medicience (catalog number: MD12015). High-fat feeding protocol: Mice were started on a gradual transition to the high-fat diet at week 5 and began formal feeding on the high-fat diet at week 6.

2. Cholesterol blood test in male mice

Figure 2. Serum lipid biochemical indicators of male B6J-Apoe KO and wild-type (WT) mice on normal diet and high-fat diet (HFD) conditions. Data showed that under normal diet conditions, compared with wild-type mice, male B6J-Apoe KO mice had different degrees of increases in triglyceride (TRIG), cholesterol (CHOL), and low-density lipoprotein (LDL-C) levels in their bodies. High-fat diet further increased the levels of these indicators in male B6J-Apoe KO mice. The levels of high-density lipoprotein (HDL-C) in male B6J-Apoe KO mice and wild-type (WT) mice were not significantly different.

3. Cholesterol blood test in female mice

Figure 3. Serum lipid biochemical indicators of female B6J-Apoe KO and wild-type (WT) mice on normal diet and high-fat diet (HFD) conditions. Under normal diet conditions, compared with wild-type mice, female B6J-Apoe KO mice had significantly elevated levels of cholesterol (CHOL) and low-density lipoprotein (LDL-C). High-fat diet further increased the levels of cholesterol (CHOL) and low-density lipoprotein (LDL-C) in female B6J-Apoe KO mice. The levels of high-density lipoprotein (HDL-C) and triglyceride (TRIG) in female B6J-Apoe KO mice and wild-type (WT) mice were not significantly different.

4. Aortic pathology in male B6J-Apoe KO mice

Figure 4. Detection of atherosclerotic plaques in the aorta of male B6J-Apoe KO mice on normal diet (ND) and high-fat diet (HFD) conditions. Male B6J-Apoe KO mice can spontaneously form atherosclerotic plaques in the aorta after 10 weeks on a normal diet, with mild symptoms. After induction by high-fat diet feeding, the atherosclerotic plaques in the aorta were exacerbated, and the symptoms became more obvious after week 12, continued to worsen at week 14, and reached the late stage of pathological phenotype at week 16.

5. Aortic pathology in female B6J-Apoe KO mice

Figure 5. Detection of atherosclerotic plaques in the aorta of female B6J-Apoe KO mice on normal diet (ND) and high-fat diet (HFD) conditions. Female B6J-Apoe KO mice can spontaneously form atherosclerotic plaques in the aorta after 12 weeks on a normal diet, with mild symptoms. After induction by high-fat diet feeding, the atherosclerotic plaques in the aorta were exacerbated, and the symptoms became more obvious after week 14 and continued to worsen at week 16.

  • 6. Oil Red O staining of the aorta


    Figure     6. Oil Red O staining results for B6J-Apoe KO mice and wild-type mice (WT) under chow diet (CD) and high-fat diet (HFD) conditions. The red color indicates positive fat staining. The results show that wild-type mice, after 20 weeks of both chow and high-fat diets, exhibited no significant arterial lesions. However, B6J-Apoe KO mice, following a high-fat diet, showed noticeable fat accumulation near the aortic arch, with a more severe phenotype after 20 weeks. Similarly, B6J-Apoe KO mice, after a chow diet, also exhibited spontaneous atherosclerosis, which worsened after 20 weeks.

    • 7. Oil Red O staining of cardiac valves


    •


      Figure 7      . Oil Red O staining of cardiac valves for B6J-Apoe KO mice and wild-type mice (WT) under chow diet (CD) and high-fat diet (HFD) conditions. The results show that wild-type mice, after 20 weeks of both chow and high-fat diets, exhibited no fat accumulation near the cardiac valves. However, B6J-Apoe KO mice, following a high-fat diet, showed noticeable fat accumulation near the cardiac valves, with a more severe phenotype after 20 weeks. Similarly, B6J-Apoe KO mice also exhibited fat accumulation under a chow diet, which worsened after 20 weeks.

References

[1] Huang Y, Mahley RW. Apolipoprotein E: structure and function in lipid metabolism, neurobiology, and Alzheimer's diseases. Neurobiol Dis. 2014 Dec;72 Pt A:3-12.
[2] Mahley RW, Weisgraber KH, Huang Y. Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer's disease to AIDS. J Lipid Res. 2009 Apr;50 Suppl(Suppl):S183-8.
[3] Wang H, Kulas JA, Wang C, Holtzman DM, Ferris HA, Hansen SB. Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol. Proc Natl Acad Sci U S A. 2021 Aug 17;118(33):e2102191118.
[4] Serrano-Pozo A, Das S, Hyman BT. APOE and Alzheimer's disease: advances in genetics, pathophysiology, and therapeutic approaches. Lancet Neurol. 2021 Jan;20(1):68-80.
[5] Yin C, Ackermann S, Ma Z, Mohanta SK, Zhang C, Li Y, Nietzsche S, Westermann M, Peng L, Hu D, Bontha SV, Srikakulapu P, Beer M, Megens RTA, Steffens S, Hildner M, Halder LD, Eckstein HH, Pelisek J, Herms J, Roeber S, Arzberger T, Borodovsky A, Habenicht L, Binder CJ, Weber C, Zipfel PF, Skerka C, Habenicht AJR. ApoE attenuates unresolvable inflammation by complex formation with activated C1q. Nat Med. 2019 Mar;25(3):496-506.