hIFNAR1/R2-EC Mouse
製品名
hIFNAR1/R2-EC Mouse
製品ID
C001998
系統名
C57BL/6NCya-Ifnar1tm2(hIFNAR1)Ifnar2tm1(hIFNAR2)/Cya
背景情報
C57BL/6NCya
状況
このマウス系統を論文で使用する場合は、「hIFNAR1/R2-EC Mouse（カタログ番号C001998）はサイアジェンから購入しました。」と引用してください。
製品タイプ
年齢
遺伝子型
性別
数量
遺伝子別名
AVP, IFRC, IFNAR, IFNBR, IMD106, IFN-alpha-REC, IFN-R, IMD45, IFNABR, IFNARB, IFN-R-2
染色体
Chr 21, Chr 21
MGI ID
さらに
系統詳細
Interferons (IFNs) are a multigene family of cytokines that play critical roles in antiviral defense and regulation of tumor immunity [1]. Human IFNs are classified into type I, II, and III based on receptor-binding specificity. Among them, type I IFNs comprise nearly 20 subtypes, whose signaling relies on a heterodimeric receptor composed of IFNAR1 and IFNAR2 subunits. Ligand binding triggers the JAK-STAT signaling pathway, inducing the expression of interferon-stimulated genes (ISGs) and thereby executing antiviral and immunomodulatory functions [2-3]. IFN-α2, an early discovered and well‑characterized type I IFN subtype, has been approved for clinical use against chronic hepatitis B virus (HBV) infection and certain tumors since the 1990s. However, its clinical application is limited by low response rates and severe side effects [4-5]. Furthermore, the interaction between human IFN and IFNAR is species‑specific, rendering wild-type mice largely unresponsive to human type I IFN — a major obstacle for dissecting the functions of human IFN subtypes and developing novel interferon‑based therapeutics [6].
The hIFNAR1/R2-EC mouse model harbors chimeric receptors (IFNAR-hEC) consisting of the humanized IFNAR extracellular domain and murine transmembrane and intracellular domains, while preserving the regulatory elements and signal peptide regions of the murine Ifnar1/2 loci. Using gene editing, the region from aa.27 in exon 2 to partial intron 2 of the mouse Ifnar1 was replaced with the IFNAR1 chimera CDS, and the region from aa.22 in exon 3 to partial intron 3 of the mouse Ifnar2 was replaced with the IFNAR2 chimera CDS. This immunocompetent mouse model responds robustly to human type I IFNs. It enables characterization of the differential activation of the JAK-STAT pathway by human IFN-α2, α14, and other subtypes, and supports in vivo validation of the long‑term antiviral efficacy of clinically used pegylated human IFN‑α2 in HBV replication models. It therefore provides a powerful platform for investigating the antiviral and immunomodulatory mechanisms of human type I IFN subtypes and for preclinical evaluation of interferon‑based drugs [7].
参考文献
Isaacs A, Lindenmann J. Virus interference. I. The interferon. By A. Isaacs and J. Lindenmann, 1957. J Interferon Res. 1987 Oct;7(5):429-38.
González-Navajas JM, Lee J, David M, Raz E. Immunomodulatory functions of type I interferons. Nat Rev Immunol. 2012 Jan 6;12(2):125-35.
Hoffmann HH, Schneider WM, Rice CM. Interferons and viruses: an evolutionary arms race of molecular interactions. Trends Immunol. 2015 Mar;36(3):124-38.
Lok AS, Lai CL, Wu PC, Leung EK. Long-term follow-up in a randomised controlled trial of recombinant alpha 2-interferon in Chinese patients with chronic hepatitis B infection. Lancet. 1988 Aug 6;2(8606):298-302.
Fanning GC, Zoulim F, Hou J, Bertoletti A. Therapeutic strategies for hepatitis B virus infection: towards a cure. Nat Rev Drug Discov. 2019 Nov;18(11):827-844.
Harari D, Abramovich R, Zozulya A, Smith P, Pouly S, Köster M, Hauser H, Schreiber G. Bridging the species divide: transgenic mice humanized for type-I interferon response. PLoS One. 2014 Jan 9;9(1):e84259.
Li Y, Ashuo A, Hao M, Li Y, Ye J, Liu J, Hua T, Fang Z, Li J, Yuan Z, Chen J. An extracellular humanized IFNAR immunocompetent mouse model for analyses of human interferon alpha and subtypes. Emerg Microbes Infect. 2024 Dec;13(1):2287681.
系統作製戦略
Using gene editing, the region from aa.27 in exon 2 to partial intron 2 of the mouse Ifnar1 was replaced with the IFNAR1 chimera CDS, and the region from aa.22 in exon 3 to partial intron 3 of the mouse Ifnar2 was replaced with the IFNAR2 chimera CDS.
Figure 1. Gene editing strategy of hIFNAR1/R2-EC mice.
*IFNAR1 chimera CDS (Extracellular Domain of Human IFNAR1 + Transmembrane and Cytoplasmic of Mouse Ifnar1)
*IFNAR2 chimera CDS (Extracellular Domain of Human IFNAR2 + Transmembrane and Cytoplasmic of Mouse Ifnar2)
適用分野
Investigation of the molecular mechanisms underlying antiviral and immunomodulatory functions of human type I IFN subtypes;
Basic and translational research on IFN‑related diseases, such as chronic hepatitis B virus (HBV) infection and tumors;
Preclinical evaluation of interferon‑based pharmaceuticals, including activity screening of various IFN subtypes, efficacy validation of long‑acting interferon formulations, and assessment of synergistic effects of IFN combination therapies.
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