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C57BL/6JCya-Il1rapem1/Cya
Common Name:
Il1rap-KO
Product ID:
S-KO-02638
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
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Basic Information
Strain Name
Il1rap-KO
Strain ID
KOCMP-16180-Il1rap-B6J-VA
Gene Name
Il1rap
Product ID
S-KO-02638
Gene Alias
6430709H04Rik; IL-1RAcP
Background
C57BL/6JCya
NCBI ID
16180
Modification
Conventional knockout
Chromosome
16
Phenotype
MGI:104975
Document
Click here to download >>
Application
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Rare Disease Data Center >>
Note
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Il1rapem1/Cya mice (Catalog S-KO-02638) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000096129
NCBI RefSeq
NM_001159318
Target Region
Exon 3~4
Size of Effective Region
~4.5 kb
Detailed Document
Click here to download >>
Overview of Gene Research
Il1rap, the interleukin-1 receptor accessory protein, is an essential coreceptor for signaling through the IL-1, IL-33, and IL-36 receptors. It is involved in multiple signaling pathways such as TNF, NF-κB, IL-17, and JAK/STAT, and also plays a role in immune cell differentiation pathways [2,4,5,8]. It is of great biological importance as it is associated with various physiological and pathological processes. Genetic models, like gene knockout (KO) mouse models, are valuable for studying its functions.

In Ewing sarcoma, IL1RAP is induced by oncogenic fusions, and its inactivation triggers anoikis and impedes metastatic dissemination, as it maintains cyst(e)ine and glutathione pools for redox homeostasis and anoikis resistance. It is minimally expressed in normal tissues, making it a promising target for immunotherapy [1]. In acute myeloid leukemia (AML), IL1RAP is highly expressed on bulk blasts and leukemic stem cells but not on normal hematopoietic stem cells. Targeting IL1RAP via RNA interference, genetic deletion, or antibodies inhibits AML pathogenesis in vitro and in vivo without affecting healthy hematopoiesis. IL1RAP also physically interacts with and mediates signaling through FLT3 and c-KIT in AML [3,7]. In systemic sclerosis, targeting IL1RAP with an antibody reduces dermal and pulmonary fibrosis in mouse models, and RNAseq analyses show its inhibition affects inflammation and fibrosis-related processes [4]. In viral and autoimmune myocarditis, IL1RAP blockade with a monoclonal antibody reduces disease severity and preserves cardiac function in mouse models [5]. In pancreatic ductal adenocarcinoma, blocking IL1RAP on cancer-associated fibroblasts inhibits IL-1-induced chemokine secretion and recruitment of neutrophils and monocytes, counteracting the immunosuppressive microenvironment [6]. In atherosclerosis, IL1RAP blockade in mice reduces plaque size, limits leucocyte accumulation, and reduces chemokine production related to plaque inflammation [8].

In conclusion, Il1rap is crucial for signaling through multiple cytokine receptors and is involved in various biological processes. Model-based research, especially KO mouse models, has revealed its significant roles in diseases such as Ewing sarcoma, AML, systemic sclerosis, myocarditis, pancreatic ductal adenocarcinoma, and atherosclerosis. Understanding Il1rap functions provides potential therapeutic targets for these diseases.

References:

1. Zhang, Hai-Feng, Hughes, Christopher S, Li, Wei, Dimitrov, Dimiter S, Sorensen, Poul H. 2021. Proteomic Screens for Suppressors of Anoikis Identify IL1RAP as a Promising Surface Target in Ewing Sarcoma. In Cancer discovery, 11, 2884-2903. doi:10.1158/2159-8290.CD-20-1690. https://pubmed.ncbi.nlm.nih.gov/34021002/

2. Badi, Yusef Eamon, Salcman, Barbora, Taylor, Adam, Bates, Stewart, Adcock, Ian M. 2022. IL1RAP expression and the enrichment of IL-33 activation signatures in severe neutrophilic asthma. In Allergy, 78, 156-167. doi:10.1111/all.15487. https://pubmed.ncbi.nlm.nih.gov/35986608/

3. Zhang, Yi, Park, Miso, Ghoda, Lucy Y, Williams, John C, Marcucci, Guido. 2024. IL1RAP-specific T cell engager depletes acute myeloid leukemia stem cells. In Journal of hematology & oncology, 17, 67. doi:10.1186/s13045-024-01586-x. https://pubmed.ncbi.nlm.nih.gov/39143574/

4. Grönberg, Caitríona, Rattik, Sara, Tran-Manh, Cuong, Distler, Jörg Hw, Trinh-Minh, Thuong. 2024. Combined inhibition of IL-1, IL-33 and IL-36 signalling by targeting IL1RAP ameliorates skin and lung fibrosis in preclinical models of systemic sclerosis. In Annals of the rheumatic diseases, 83, 1156-1168. doi:10.1136/ard-2023-225158. https://pubmed.ncbi.nlm.nih.gov/38594058/

5. Lema, Diego A, Jakobsson, Gabriel, Daoud, Abdel, Schiopu, Alexandru, Čiháková, Daniela. 2024. IL1RAP Blockade With a Monoclonal Antibody Reduces Cardiac Inflammation and Preserves Heart Function in Viral and Autoimmune Myocarditis. In Circulation. Heart failure, 17, e011729. doi:10.1161/CIRCHEARTFAILURE.124.011729. https://pubmed.ncbi.nlm.nih.gov/39513273/

6. Hansen, Nils, Peña-Martínez, Pablo, Skoog, Petter, Liberg, David, Järås, Marcus. 2024. Blocking IL1RAP on cancer-associated fibroblasts in pancreatic ductal adenocarcinoma suppresses IL-1-induced neutrophil recruitment. In Journal for immunotherapy of cancer, 12, . doi:10.1136/jitc-2024-009523. https://pubmed.ncbi.nlm.nih.gov/39694705/

7. Mitchell, Kelly, Barreyro, Laura, Todorova, Tihomira I, Gritsman, Kira, Steidl, Ulrich. 2018. IL1RAP potentiates multiple oncogenic signaling pathways in AML. In The Journal of experimental medicine, 215, 1709-1727. doi:10.1084/jem.20180147. https://pubmed.ncbi.nlm.nih.gov/29773641/

8. Mulholland, Megan, Depuydt, Marie A C, Jakobsson, Gabriel, Slütter, Bram, Engelbertsen, Daniel. . Interleukin-1 receptor accessory protein blockade limits the development of atherosclerosis and reduces plaque inflammation. In Cardiovascular research, 120, 581-595. doi:10.1093/cvr/cvae046. https://pubmed.ncbi.nlm.nih.gov/38563353/

Quality Control Standard
Sperm Test

Pre-cryopreservation: Measurement of sperm concentration, determination of sperm viability.

Post-cryopreservation: A vial of cryopreserved sperms is selected for in-vitro fertilization from each batch.

Environmental Standards:SPF
Available Region:Global
Source:Cyagen
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