B6-hIL6/IL6RA Mouse
Product Name
B6-hIL6/IL6RA Mouse
Product ID
C001607
Strain Name
C57BL/6NCya-Il6em1(hIL6)Il6raem1(hIL6RA)/Cya
Backgroud
C57BL/6NCya
Status
When using this mouse strain in a publication, please cite “B6-hIL6/IL6RA Mouse (Catalog C001607) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
IL6
Gene Alias
CDF, HGF, HSF, BSF2, IL-6, BSF-2, IFNB2, IFN-beta-2
NCBI ID
Chromosome
Chr 7 (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]. IL-6 has a broad impact on both immune and non-immune cells. In CD4+ T helper (Th) cells, IL-6 drives the differentiation of activated naïve Th cells into IL-17 and IL-22 expressing Th17 and Th22 cells, which are crucial for anti-bacterial and anti-fungal defense. Conversely, IL-6 inhibits the differentiation of CD4+ T regulatory cells, which play a key role in restraining inflammatory responses. In hepatocytes, IL-6 induces the expression of inflammation-induced acute phase proteins, including C-reactive protein (CRP) [1]. Research has shown that the IL-6 pathway is crucial for maintaining homeostasis and is involved in the dysregulation seen in many diseases. Antibody drugs targeting the IL-6/IL-6 receptor signaling pathway have become innovative therapies for autoimmune diseases and cancers [2-5].
The B6-hIL6/IL6RA mice are a double-gene humanized model obtained by breeding B6-hIL6 mice (Catalog No. C001605) with B6-hIL6RA mice (Catalog No. C001606). This model can be used in researching autoimmune diseases, inflammation-related diseases, cancer, and infectious diseases. It is also useful for the development, screening, and evaluation of IL6/IL6RA-targeted drugs.
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.
Weber R, Groth C, Lasser S, Arkhypov I, Petrova V, Altevogt P, Utikal J, Umansky V. IL-6 as a major regulator of MDSC activity and possible target for cancer immunotherapy. Cell Immunol. 2021 Jan;359:104254.
Pandolfi F, Franza L, Carusi V, Altamura S, Andriollo G, Nucera E. Interleukin-6 in Rheumatoid Arthritis. Int J Mol Sci. 2020 Jul 23;21(15):5238.
The application and development of IL-6 pathway inhibitors[J]. International Journal of Biologicals, 2020, 43(5): 239-242.
Strain Strategy
Figure 1. Diagram of the gene editing strategy for the generation of B6-hIL6 mice. The sequences from the ATG start codon to the TAG stop codon of the endogenous mouse Il6 gene were replaced with the sequences from the ATG start codon to the TAG stop codon of the human IL6 gene.
Figure 2. Diagram of the gene editing strategy for the generation of B6-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.
Application Area
Research on autoimmune diseases, inflammation-related diseases, cancer, and infectious diseases;
Preclinical studies on the development, screening, and evaluation of IL6/IL6RA-targeted drugs.
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