B6-hIL4RA Mice

Catalog Number: C001629

Strain Name: C57BL/6NCya-Il4raem1(hIL4R)/Cya

Genetic Background: C57BL/6NCya

Reproduction: Homozygote x Homozygote

 

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].

B6-hIL4RA mice are humanized models generated using gene editing technology by replacing the extracellular domain of the mouse Il4ra (aa.28~217) with the corresponding human IL4R extracellular domain (aa.28~216), while retaining the murine signal peptide (aa.1~25). Homozygous B6-hIL4RA mice are viable and fertile. This model is 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-4Rα.

 

Strain Strategy


Figure 1. Gene editing strategy of B6-hIL4RA mice. The extracellular domain of the mouse Il4ra (aa.28~217) is replaced with the corresponding human IL4R extracellular domain (aa.28~216), while retaining the murine signal peptide (aa.1~25).

 

Strain Application

  • Investigation of immune regulation and Th2 responses, allergic diseases, parasitic infections, and tumor immunology.
  • Preclinical development, screening, and efficacy evaluation of IL-4Rα-targeted therapeutic agents.
  • Studies on inflammation and autoimmune diseases

 

Validation Data

1. RT-qPCR


Figure 2. Detection of gene expression in the spleen, lung, and thymus of homozygous B6-hIL4RA mice and wild-type (WT) mice (7-week-old, female, n = 4). The results of RT-qPCR showed that the expression of the human IL4RA gene was detected in the spleen, lung, and thymus of homozygous B6-hIL4RA mice, while the expression of mouse Il4ra gene was not detected. Conversely, the expression of the mouse Il4ra gene was detected in WT mice, but the expression of the human IL4RA gene was not detected. The above data indicate that the human IL4RA gene is successfully expressed in the spleen, lung, and thymus of B6-hIL4RA mice, and the mouse Il4ra gene is not expressed.

 

2. ELISA


Figure 3. Expression of human-specific IL4RA protein in the serum of B6-hIL4RA mice and wild-type (WT) mice. The serum samples were collected from WT mice and B6-hIL4RA mice respectively. The expression level of human IL4RA was detected by enzyme-linked immunosorbent assay (ELISA) using a human IL-4R-specific ELISA kit. The results showed that significant expression of human IL4RA protein was detected in the serum of homozygous and heterozygous B6-hIL4RA mice, while no expression of human IL4RA protein was observed in the serum of WT mice. In addition, in terms of the expression level of hIL4RA, the expression amount in homozygous B6-hIL4RA mice was approximately twice that in heterozygous mice.


References
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[3]Bankaitis KV, Fingleton B. Targeting IL4/IL4R for the treatment of epithelial cancer metastasis. Clin Exp Metastasis. 2015 Dec;32(8):847-56.
[4]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.
[5]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.
[6]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.
[7]Napolitano M, Ruggiero A, Patruno C. Dupilumab-associated inflammatory arthritis: a literature review. Clin Exp Dermatol. 2024 Mar 21;49(4):307-312.