B6-hIL4 Mice

Catalog Number: C001628

Strain Name: C57BL/6NCya-Il4em1(hIL4)/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-4 as a promising therapeutic target.

B6-hIL4 mice are humanized models generated using gene editing technology by replacing the sequences from the ATG start codon to the TAG stop codon of the endogenous mouse Il4 gene with the sequences from the ATG start codon to the TGA stop codon of the human IL4 gene. Homozygous B6-hIL4 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-4.

 

Strain Strategy


Figure 1. Gene editing strategy of B6-hIL4 mice. The sequences from the ATG start codon to the TAG stop codon of the endogenous mouse Il4 gene are replaced with the sequences from the ATG start codon to the TGA stop codon of the human IL4 gene.

 

Strain Application

  • Investigation of immune regulation and Th2 responses, allergic diseases, parasitic infections, and tumor immunology.
  • Preclinical development, screening, and efficacy evaluation of IL4-targeted therapeutic agents.
  • Studies on inflammation and autoimmune diseases

 

Validation Data

1. Gene Expression


Figure 2. Detection of gene expression in the spleen, thymus, and lymph nodes of wild-type (WT) mice and B6-hIL4 mice (12-week-old, homozygous, male, n = 3). The RT-qPCR results showed that the human IL4 gene was expressed in the spleen, thymus, and lymph nodes of B6-hIL4 mice, and the mouse Il4 gene was not expressed. In contrast, WT mice only expressed the mouse Il4 gene (Mean ± SD; ND: Not Detected).

 

2. Detection of Human Protein Expression


Figure 2. Expression of human-specific IL-4 protein in the serum of wild-type (WT) and homozygous B6-hIL4 mice (6–10 weeks old) following T cell activation with anti-CD3ε treatment in vivo. Under normal conditions, IL-4 levels in mouse serum are low and difficult to detect. Activation of T cells by intraperitoneal injection of anti-CD3ε enhances IL-4 production in vivo, facilitating its detection. At 1.5 hours post-T cell activation, serum was collected from WT and homozygous B6-hIL4 mice and analyzed for human IL-4 expression using a human IL-4-specific ELISA kit via enzyme-linked immunosorbent assay (ELISA). The data demonstrate that serum levels of human IL-4 in B6-hIL4 mice significantly increase following T cell activation, whereas no human IL-4 protein is detected in the serum of WT mice (n = 3).


References
[1]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.
[2]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.
[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.