B6-hIL4/hIL4RA Mouse
Product Name
B6-hIL4/hIL4RA Mouse
Product ID
C001834
Strain Name
C57BL/6NCya-Il4em1(hIL4)Il4raem1(hIL4R)/Cya
Backgroud
C57BL/6NCya
Status
When using this mouse strain in a publication, please cite “B6-hIL4/hIL4RA Mouse (Catalog C001834) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
IL4 & IL4R
Gene Alias
BSF1, IL-4, BCGF1, BSF-1, BCGF-1, CD124, IL4RA, IL-4RA
NCBI ID
Chromosome
Chr 5 (Human), Chr 16 (Human)
MGI ID
Datasheet
Strain Description
Interleukin-4 (IL-4) and its receptor, IL-4R, are pivotal regulators of immune responses and inflammation. The IL4 gene encodes the IL-4 cytokine, a multifunctional protein predominantly secreted by Th2 cells, mast cells, and eosinophils, while the IL4R gene encodes the IL-4 receptor, which is expressed on a variety of immune cells, including B cells, T cells, macrophages, and endothelial cells. IL-4 binds to IL-4R, which exists in two distinct forms: Type I (comprising IL-4Rα and the common γ-chain) and Type II (comprising IL-4Rα and IL-13Rα1) [1]. This interaction activates the JAK-STAT signaling pathway, driving Th2 cell differentiation, B cell class switching to IgE, and anti-inflammatory responses. The IL-4/IL-4R signaling axis is critically implicated in allergic diseases such as asthma, atopic dermatitis, and allergic rhinitis, as well as in parasitic infections and certain cancers [2-5]. Dysregulation of this pathway underlies various pathological conditions, positioning IL-4R as a promising therapeutic target. For instance, dupilumab, a monoclonal antibody targeting IL-4Rα, has been approved for the treatment of atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyps, underscoring the therapeutic potential of modulating this pathway [6-7].
The B6-hIL4/hIL4RA mouse model is generated by crossing IL4 humanized mice (Catalog Number: C001628) with IL4R humanized mice (Catalog Number: C001629), resulting in a dual-humanized model. This model faithfully recapitulates the human IL-4/IL-4R signaling pathway, making it an invaluable tool for studying allergic diseases (e.g., asthma and atopic dermatitis), Th2 immune responses, parasitic infections, tumor immunology, and chronic inflammation. Furthermore, it serves as a robust preclinical platform for evaluating the efficacy and mechanisms of therapeutic agents targeting the IL-4/IL-4Rα pathway.
Reference
Gandhi NA, Bennett BL, Graham NM, Pirozzi G, Stahl N, Yancopoulos GD. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016 Jan;15(1):35-50.
Oetjen LK, Mack MR, Feng J, Whelan TM, Niu H, Guo CJ, Chen S, Trier AM, Xu AZ, Tripathi SV, Luo J, Gao X, Yang L, Hamilton SL, Wang PL, Brestoff JR, Council ML, Brasington R, Schaffer A, Brombacher F, Hsieh CS, Gereau RW 4th, Miller MJ, Chen ZF, Hu H, Davidson S, Liu Q, Kim BS. Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch. Cell. 2017 Sep 21;171(1):217-228.e13.
Bankaitis KV, Fingleton B. Targeting IL4/IL4R for the treatment of epithelial cancer metastasis. Clin Exp Metastasis. 2015 Dec;32(8):847-56.
Davoodi P, Mahesh PA, Holla AD, Ramachandra NB. A preliminary study on the association of single nucleotide polymorphisms of interleukin 4 (IL4), IL13, IL4 receptor alpha (IL4Rα) & Toll-like receptor 4 (TLR4) genes with asthma in Indian adults. Indian J Med Res. 2015 Dec;142(6):675-80.
Choy DF, Hart KM, Borthwick LA, Shikotra A, Nagarkar DR, Siddiqui S, Jia G, Ohri CM, Doran E, Vannella KM, Butler CA, Hargadon B, Sciurba JC, Gieseck RL, Thompson RW, White S, Abbas AR, Jackman J, Wu LC, Egen JG, Heaney LG, Ramalingam TR, Arron JR, Wynn TA, Bradding P. TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma. Sci Transl Med. 2015 Aug 19;7(301):301ra129.
Muñoz-Bellido FJ, Moreno E, Dávila I. Dupilumab: A Review of Present Indications and Off-Label Uses. J Investig Allergol Clin Immunol. 2022 Apr 19;32(2):97-115.
Napolitano M, Ruggiero A, Patruno C. Dupilumab-associated inflammatory arthritis: a literature review. Clin Exp Dermatol. 2024 Mar 21;49(4):307-312.
Strain Strategy
Figure 1. B6-hIL4 Mice Strategy. The sequences from the ATG start codon to the TAG stop codon of the endogenous mouse Il4 gene were replaced with the sequences from the ATG start codon to the TGA stop codon of the human IL4 gene.
Figure 2. B6-hIL4RA Mice Strategy. The extracellular domain of the mouse Il4ra was replaced with the corresponding human IL4R extracellular domain, while retaining the murine signal peptide.
Application Area
Investigation of immune regulation and Th2 responses, allergic diseases, parasitic infections, and tumor immunology;
Preclinical development, screening, and efficacy evaluation of IL4/IL4R-targeted therapeutic agents;
Studies on inflammation and autoimmune diseases.
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