B6-hIL1RAP Mice

Catalog Number: C001631

Strain Name: C57BL/6NCya-Il1rapem1(hIL1RAP)/Cya

Genetic Background: C57BL/6NCya

Reproduction: Homozygote x Homozygote

 

Strain Description

The interleukin-1 receptor accessory protein, encoded by IL1RAP, serves as a critical co-receptor for multiple cytokine systems, notably the interleukin-1 (IL-1) family. This broadly expressed protein is essential for the formation of functional receptor complexes for IL-1, IL-33, and IL-36, thereby mediating downstream signaling pathways that drive innate immunity and inflammatory responses [1-5]. Acting as a co-receptor, IL1RAP interacts with ligand-binding receptors such as IL1R1, IL33R (IL1RL1/ST2), and IL36R, initiating MyD88-dependent signal transduction that culminates in the expression of pro-inflammatory genes and cytokines [1-5]. IL1RAP expression is observed across a range of cell types, including immune, endothelial, epithelial, and neuronal cells, as well as various tumor lineages. Perturbations in IL1RAP expression or genetic variants have been implicated in a spectrum of pathologies, encompassing inflammatory diseases such as asthma, autoimmune disorders, neurodegenerative conditions such as Alzheimer's disease, and malignancies including acute myeloid leukemia, Ewing sarcoma, pancreatic cancer, and gastric adenocarcinoma [2-4]. Consequently, IL1RAP represents a target of intense investigation for therapeutic interventions in cancer and inflammatory diseases [4-5].

B6-hIL1RAP mice are humanized models generated using gene editing technology. They are constructed by integrating the protein-coding sequence (CDS) encoding the extracellular domain of human IL1RAP protein and the intracellular domain of mouse IL1RAP protein, along with the 3'UTR of the mouse Il1rap gene, into a specific site within the mouse Il1rap gene. This process retains the endogenous gene sequence encoding the mouse signal peptide (aa.1~20). Homozygous B6-hIL1RAP mice are viable and fertile. This model can be used for studying the pathological mechanisms and therapeutic approaches of cancer and inflammatory diseases, and for the development of IL1RAP-targeted drugs.

 

Strain Strategy


Figure 1. Gene editing strategy of B6-hIL1RAP mice. The partial coding sequence of exon 2 to partial intron 2 sequence of the mouse Il1rap gene was replaced with an "Extracellular domain of Human IL1RAP CDS (aa.21-367)-Mouse Il1rap CDS (aa.368-570)-3'UTR of Mouse Il1rap-WPRE-BGH pA" cassette. The murine signal peptide (aa.1~20) of the mouse IL1RAP protein was preserved.

 

Application

  • IL1RAP-targeted drug screening, development, and evaluation;
  • Research on the pathological mechanisms and therapeutic approaches of cancer and inflammatory diseases.


References
[1]Frenay J, Bellaye PS, Oudot A, Helbling A, Petitot C, Ferrand C, Collin B, Dias AMM. IL-1RAP, a Key Therapeutic Target in Cancer. Int J Mol Sci. 2022 Nov 29;23(23):14918.
[2]Wu M, Zheng X, Huang J, Hu X. Association of IL33, IL1RL1, IL1RAP Polymorphisms and Asthma in Chinese Han Children. Front Cell Dev Biol. 2021 Dec 15;9:759542.
[3]Zettergren A, Höglund K, Kern S, Thorvaldsson V, Johan Skoog M, Hansson O, Andreasen N, Bogdanovic N, Blennow K, Skoog I, Zetterberg H. Association of IL1RAP-related genetic variation with cerebrospinal fluid concentration of Alzheimer-associated tau protein. Sci Rep. 2019 Feb 21;9(1):2460.
[4]Zarezadeh Mehrabadi A, Shahba F, Khorramdelazad H, Aghamohammadi N, Karimi M, Bagherzadeh K, Khoshmirsafa M, Massoumi R, Falak R. Interleukin-1 receptor accessory protein (IL-1RAP): A magic bullet candidate for immunotherapy of human malignancies. Crit Rev Oncol Hematol. 2024 Jan;193:104200.
[5]Zarezadeh Mehrabadi A, Aghamohamadi N, Khoshmirsafa M, Aghamajidi A, Pilehforoshha M, Massoumi R, Falak R. The roles of interleukin-1 receptor accessory protein in certain inflammatory conditions. Immunology. 2022 May;166(1):38-46.