C57BL/6JCya-Il11ra1em1flox/Cya
Common Name:
Il11ra1-flox
Product ID:
S-CKO-17494
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Il11ra1-flox
Strain ID
CKOCMP-16157-Il11ra1-B6J-VA
Gene Name
Product ID
S-CKO-17494
Gene Alias
GP130; Il-11ra; Il11ra; Il11ra2; NR1
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
4
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Il11ra1em1flox/Cya mice (Catalog S-CKO-17494) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000098132
NCBI RefSeq
NM_001163401
Target Region
Exon 4~7
Size of Effective Region
~1.5 kb
Detailed Document
Overview of Gene Research
Il11ra1, encoding the interleukin-11 receptor subunit alpha-1, is crucial for interleukin-11 (IL-11) signaling. IL-11 is a pro-inflammatory cytokine of the IL-6 family, and Il11ra1 enables IL-11 to regulate pathways like ERK-AMPK-mTORC1, which are important for cellular, tissue-and organismal-level functions and are associated with ageing, metabolism, and fibrosis-related processes [1,2,3,4,5,6,7,8].
In mouse models, deletion of Il11ra1 has shown protective effects in multiple disease conditions. In aged mice, Il11ra1 deletion protects against metabolic decline, multi-morbidity, and frailty [1]. In models of non-alcoholic steatohepatitis (NASH), Il11ra1 -/- mice had reduced steatosis, fibrosis, and inflammation compared to wild-type mice [3]. In the bleomycin mouse model of pulmonary fibrosis, Il11ra1-deleted mice, whose lung fibroblasts are unresponsive to profibrotic stimulation, are protected from fibrosis [4]. In cardiovascular fibrosis, genetic deletion of Il11ra1 protects against heart and kidney fibrosis and organ failure [5]. In hepatocyte-specific models, deletion of Il11ra1 protects against liver steatosis, fibrosis, and inflammation in NASH models [6]. In acute and chronic kidney disease models, mice with TEC-specific deletion of Il11ra1 have reduced pathogenic signaling and are protected from renal injury-induced inflammation, fibrosis, and failure [7]. In acetaminophen-induced liver injury, hepatocyte-specific deletion of Il11ra1 protects against liver injury [8]. Also, nanoparticle-mediated RNA interference targeting Il11ra1 effectively inhibits HSC activation and resolves fibrosis and inflammation in NASH models [9].
In conclusion, Il11ra1 is essential for IL-11-mediated signaling. The use of Il11ra1 gene-knockout (KO) and conditional-knockout (CKO) mouse models has revealed its significant role in various disease conditions such as ageing-related pathologies, NASH, pulmonary fibrosis, cardiovascular fibrosis, and kidney diseases. These findings suggest that targeting Il11ra1 or the IL-11/Il11ra1 axis could be a potential therapeutic strategy for treating these fibrotic and age-related diseases.
References:
1. Widjaja, Anissa A, Lim, Wei-Wen, Viswanathan, Sivakumar, Carling, David, Cook, Stuart A. 2024. Inhibition of IL-11 signalling extends mammalian healthspan and lifespan. In Nature, 632, 157-165. doi:10.1038/s41586-024-07701-9. https://pubmed.ncbi.nlm.nih.gov/39020175/
2. Zhuang, Tao, Chen, Mei-Hua, Wu, Ruo-Xi, Zuo, Jun-Li, Ruan, Cheng-Chao. 2024. ALKBH5-mediated m6A modification of IL-11 drives macrophage-to-myofibroblast transition and pathological cardiac fibrosis in mice. In Nature communications, 15, 1995. doi:10.1038/s41467-024-46357-x. https://pubmed.ncbi.nlm.nih.gov/38443404/
3. Widjaja, Anissa A, Singh, Brijesh K, Adami, Eleonora, Schafer, Sebastian, Cook, Stuart A. 2019. Inhibiting Interleukin 11 Signaling Reduces Hepatocyte Death and Liver Fibrosis, Inflammation, and Steatosis in Mouse Models of Nonalcoholic Steatohepatitis. In Gastroenterology, 157, 777-792.e14. doi:10.1053/j.gastro.2019.05.002. https://pubmed.ncbi.nlm.nih.gov/31078624/
4. Ng, Benjamin, Dong, Jinrui, D'Agostino, Giuseppe, Schafer, Sebastian, Cook, Stuart A. . Interleukin-11 is a therapeutic target in idiopathic pulmonary fibrosis. In Science translational medicine, 11, . doi:10.1126/scitranslmed.aaw1237. https://pubmed.ncbi.nlm.nih.gov/31554736/
5. Schafer, Sebastian, Viswanathan, Sivakumar, Widjaja, Anissa A, Sin, Kenny Y K, Cook, Stuart A. 2017. IL-11 is a crucial determinant of cardiovascular fibrosis. In Nature, 552, 110-115. doi:10.1038/nature24676. https://pubmed.ncbi.nlm.nih.gov/29160304/
6. Dong, Jinrui, Viswanathan, Sivakumar, Adami, Eleonora, Cook, Stuart A, Widjaja, Anissa A. 2021. Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH. In Nature communications, 12, 66. doi:10.1038/s41467-020-20303-z. https://pubmed.ncbi.nlm.nih.gov/33397952/
7. Widjaja, Anissa A, Viswanathan, Sivakumar, Shekeran, Shamini G, Coffman, Thomas M, Cook, Stuart A. 2022. Targeting endogenous kidney regeneration using anti-IL11 therapy in acute and chronic models of kidney disease. In Nature communications, 13, 7497. doi:10.1038/s41467-022-35306-1. https://pubmed.ncbi.nlm.nih.gov/36470928/
8. Widjaja, Anissa A, Dong, Jinrui, Adami, Eleonora, Schafer, Sebastian, Cook, Stuart A. . Redefining IL11 as a regeneration-limiting hepatotoxin and therapeutic target in acetaminophen-induced liver injury. In Science translational medicine, 13, . doi:10.1126/scitranslmed.aba8146. https://pubmed.ncbi.nlm.nih.gov/34108253/
9. Zhang, Chenshuang, Teng, Yilong, Li, Fengqiao, Xu, Xiaoyang, Zhang, Xue-Qing. 2023. Nanoparticle-Mediated RNA Therapy Attenuates Nonalcoholic Steatohepatitis and Related Fibrosis by Targeting Activated Hepatic Stellate Cells. In ACS nano, 17, 14852-14870. doi:10.1021/acsnano.3c03217. https://pubmed.ncbi.nlm.nih.gov/37490628/
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