huIL6/hIL6RA/Apoe-KO Mouse
Product Name
huIL6/hIL6RA/Apoe-KO Mouse
Product ID
C002139
Strain Name
C57BL/6Cya-Il6em1(hIL6)Il6raem1(hIL6RA)Apoeem1/Cya
Background
C57BL/6Cya
Status
When using this mouse strain in a publication, please cite “huIL6/hIL6RA/Apoe-KO Mouse (Catalog C002139) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Standard products are sold as live mice derived from cryorecovery or expansion. Frozen materials are available upon request. Pricing and lead times depend on real-time inventory.
Gene Name
Apoe & IL6 & IL6R
Gene Alias
Apo-E, CDF, HGF, HSF, BSF2, IL-6, BSF-2, IFNB2, IFN-beta-2, IL6Q, gp80, CD126, HIES5, IL-6R, IL6RA, IL6RQ, IL-1Ra, IL-6RA, IL6QTL, IL-6R-1
NCBI ID
Chromosome
Chr 7 (Mouse), Chr 7 (Human), Chr 1 (Human)
MGI ID
Datasheet
Strain Description
Interleukin-6 (IL-6) is a cytokine that plays a crucial role in inflammation and B cell maturation. It is primarily produced and secreted into the serum at sites of acute and chronic inflammation, inducing inflammatory responses through the interleukin-6 receptor alpha (IL-6Rα). The IL6RA (IL6R, also known as CD126) gene encodes a subunit of the interleukin-6 (IL-6) receptor complex. The IL-6 receptor is a protein complex composed of the IL6RA protein and the interleukin-6 signal transducer (IL6ST/GP130/IL6-beta). This receptor subunit is shared by many other cytokines. The expression of IL-6R is primarily restricted to hepatocytes, leukocytes, and megakaryocytes. Upon binding to IL-6Rα, IL-6 interacts with two GP130 molecules to form a hexameric complex in a 2:2:2 configuration [1]. Once the IL-6 receptor complex is activated, multiple downstream events allow IL-6 to mediate its diverse effects. These include the pathways of the GTPase Ras and its effector Raf, the mitogen-activated protein kinase cascade that controls cellular proliferation and differentiation, and the pathways involving tyrosine kinases of the Jak family and transcription factors of the STAT family [2].
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 [3]. 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 [4]. In peripheral tissues, ApoE is primarily produced by the liver and macrophages and mediates cholesterol metabolism. In the central nervous system, ApoE is produced mainly by astrocytes and is the major cholesterol carrier in the brain. ApoE is essential for transporting cholesterol from astrocytes to neurons [3-6]. In addition, ApoE forms a complex with activated C1q, becoming a checkpoint inhibitor target of the classical complement pathway [7].
The huIL6/hIL6RA/Apoe-KO mouse is a combined genetically modified model generated by crossing the huIL6 mouse (Catalog No.: C001605), the hIL6RA mouse (Catalog No.: C001606), and the Apoe-KO(6J) mouse (Catalog No.: C001507). The huIL6/hIL6RA/Apoe-KO mouse can be utilized for the screening, pharmacodynamic evaluation, safety assessment, and mechanism of action studies of IL6/IL6RA-targeted therapeutics. With the Apoe knockout background, the model can also be used for research on hypercholesterolemia and atherosclerosis, providing a preclinical research tool for exploring the effects of IL6/IL6RA-targeted interventions in relevant disease settings.
Reference
Chen YH, Spencer S, Laurence A, Thaventhiran JE, Uhlig HH. Inborn errors of IL-6 family cytokine responses. Curr Opin Immunol. 2021 Oct;72:135-145.
Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol. 2015 May;16(5):448-57.
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.
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.
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.
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.
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.
Strain Strategy
The huIL6/hIL6RA/Apoe-KO mouse is a combined genetically modified model generated by crossing the huIL6 mouse (Catalog No.: C001605), the hIL6RA mouse (Catalog No.: C001606), and the Apoe-KO(6J) mouse (Catalog No.: C001507).
Figure 1. Diagram of the gene editing strategy for the generation of huIL6 mice. The sequences from the start codon to the stop codon of the endogenous mouse Il6 gene were replaced with the sequences from the start codon to the stop codon of the human IL6 gene.
Figure 2. Diagram of the gene editing strategy for the generation of hIL6RA mice. The partial exon 1 coding region of mouse Il6ra was replaced with the Kozak-IL6R Chimera CDS-3’UTR of Mouse Il6ra-WPRE-BGH pA cassette.
*IL6R Chimera CDS: Signal Peptide and Extracellular Domain of Human IL6R + Transmembrane and Cytoplasmic Domain of Mouse Il6ra.
Figure 3. Diagram of the gene editing strategy for the generation of Apoe-KO(6J) mice. The exons 2-4 of the Apoe gene in C57BL/6JCya mice were knocked out using gene editing technology.
Application Area
Screening, pharmacodynamic evaluation, safety evaluation, and mechanism of action studies of drugs targeting IL6/IL6RA;
Research on hypercholesterolemia and atherosclerosis.
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