huIL33/huIL33R Mouse
Product Name
huIL33/huIL33R Mouse
Product ID
C002039
Strain Name
C57BL/6NCya-Il33em1(hIL33)Il1rl1em1(hIL1RL1)/Cya
Backgroud
C57BL/6NCya
Status
When using this mouse strain in a publication, please cite “huIL33/huIL33R Mouse (Catalog C002039) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
IL33 & IL1RL1
Gene Alias
DVS27, IL1F11, NF-HEV, NFEHEV, C9orf26, T1, ST2, DER4, ST2L, ST2V, FIT-1, IL33R
NCBI ID
Chromosome
Chr 9 (Human), Chr 2 (Human)
MGI ID
Datasheet
Strain Description
IL33 encodes interleukin-33 (IL-33), a member of the IL-1 cytokine family that functions as an important endogenous alarmin in the immune system [1]. IL-33 is mainly released by barrier tissue cells, such as epithelial cells and endothelial cells, under conditions including mechanical injury, pathogen infection, or oxidative stress. It binds to the IL1RL1/ST2 receptor complex expressed on the surface of various immune cells, including Th2 cells, mast cells, basophils, eosinophils, and group 2 innate lymphoid cells (ILC2s), thereby initiating downstream signaling cascades.
Interleukin-1 receptor-like protein 1 (IL1RL1), also known as ST2 or IL33R, is a member of the interleukin-1 receptor superfamily and serves as the specific receptor for IL-33, playing a critical role in inflammatory responses and immune regulation [2]. The IL1RL1 gene encodes two major protein isoforms: the transmembrane receptor ST2L and the soluble receptor sST2. Functional ST2L is primarily expressed on the surface of various cell types, including immune cells (such as mast cells, helper T cells, and eosinophils), epithelial cells, and endothelial cells [2]. Upon IL-33 stimulation, ST2L activation triggers downstream inflammatory signaling pathways, including NF-κB and MAPK pathways, promoting the release of cytokines and chemokines and participating in various biological processes, including type 2 inflammatory responses, fibrosis, and tumor microenvironment regulation [2-5]. The IL-33/IL1RL1 signaling pathway exhibits complex roles in cancer, potentially promoting tumor cell proliferation, metastasis, and angiogenesis, while also activating antitumor immunity and suppressing tumor growth [3].
The huIL33/huIL33R mouse is a dual-target humanized model obtained by crossing the huIL33 mouse (Catalog No.: C001722) with the huIL1RL1(IL33R) mouse (Catalog No.: C001632). This model is applicable for studying the pathogenesis of inflammatory diseases, including asthma, atopic dermatitis (AD), allergic rhinitis, and inflammatory bowel disease (IBD), as well as tumor-related diseases. It can also be used for the screening, development, and preclinical pharmacodynamic and safety evaluation of therapeutics targeting the IL-33/IL1RL1 pathway.
Reference
Shakerian L, Kolahdooz H, Garousi M, Keyvani V, Kamal Kheder R, Abdulsattar Faraj T, Yazdanpanah E, Esmaeili SA. IL-33/ST2 axis in autoimmune disease. Cytokine. 2022 Oct;158:156015.
Griesenauer B, Paczesny S. The ST2/IL-33 Axis in Immune Cells during Inflammatory Diseases. Front Immunol. 2017 Apr 24;8:475.
Andreone S, Gambardella AR, Mancini J, Loffredo S, Marcella S, La Sorsa V, Varricchi G, Schiavoni G, Mattei F. Anti-Tumorigenic Activities of IL-33: A Mechanistic Insight. Front Immunol. 2020 Nov 30;11:571593.
Yi XM, Li M, Chen YD, Shu HB, Li S. Reciprocal regulation of IL-33 receptor-mediated inflammatory response and pulmonary fibrosis by TRAF6 and USP38. Proc Natl Acad Sci U S A. 2022 Mar 8;119(10):e2116279119.
Saikumar Jayalatha AK, Hesse L, Ketelaar ME, Koppelman GH, Nawijn MC. The central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to intervention. Pharmacol Ther. 2021 Sep;225:107847.
Strain Strategy
The huIL33/huIL33R mouse is a dual-target humanized model obtained by crossing the huIL33 mouse (Catalog No.: C001722) with the huIL1RL1(IL33R) mouse (Catalog No.: C001632).
Figure 1. Gene editing strategy of huIL33 mice. The sequences from start codon to stop codon of the endogenous mouse Il33 gene were replaced with the sequences from start codon to stop codon of the human IL33 gene.
Figure 2. Gene editing strategy of huIL1RL1(IL33R) mice. The mouse Il1rl1 signal peptide and endogenous extracellular domain were replaced with the human IL1RL1 signal peptide and extracellular domain. The murine transmembrane and cytoplasmic domains were preserved.
Application Area
Pathogenesis studies of inflammatory diseases, including asthma, atopic dermatitis (AD), allergic rhinitis, and inflammatory bowel disease (IBD), as well as tumor-related diseases;
Screening, development, and preclinical pharmacodynamic and safety evaluation of therapeutics targeting the IL-33/IL1RL1 pathway.
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