B6-hIL7R Mice

Catalog Number: C001633

Strain Name: C57BL/6NCya-Il7rem1(hIL7R)/Cya

Genetic Background: C57BL/6NCya

Reproduction: Homozygote x Homozygote

 

Strain Description

The IL7R gene encodes the interleukin-7 receptor α chain (IL-7Rα), also known as CD127, a member of the type I cytokine receptor family. Expressed on T, B, NK, monocytes, and dendritic cells, IL7R gene expression is tightly regulated by transcription factors during immune cell development, playing a critical role in early T and B cell development and homeostasis [1]. IL-7Rα forms a functional receptor complex with the common γ chain receptor (IL2RG), constituting the IL-7 receptor. This complex activates downstream signaling pathways, including JAK-STAT5 and PI3K-AKT, which upregulate Bcl-2 and cell cycle regulators, promoting lymphocyte survival, proliferation, and differentiation, essential for T and B cell maturation [1, 2]. The IL-7/IL-7Rα axis is central to maintaining peripheral T cell homeostasis, regulating memory T cell generation, and promoting thymic T cell output. It also influences NK cell development and innate lymphoid cell (ILC) maturation. Notably, IL7R gene polymorphisms are associated with autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus [1-3]. Dysregulation of IL-7R signaling is pathogenic; deficiency is linked to severe combined immunodeficiency (SCID) [4], while overexpression or aberrant activation may promote tumor growth, metastasis, and alter the tumor microenvironment [5]. Consequently, targeting the IL-7R pathway holds therapeutic potential for immune and tumor-related diseases, positioning IL-7Rα as a potential target in autoimmune diseases, immunodeficiency, and cancer [3-5].

The B6-hIL7R mouse is a humanized model constructed using gene editing technology, where the mouse IL7R endogenous extracellular domain (aa.21~239) was replaced with the human IL7R extracellular domain (aa.21~239). The murine IL7R signal peptide and cytoplasmic region (aa.1~20, aa.240~459) was preserved. Homozygous B6-hIL7R mice are viable and fertile. This model can be used for studying the pathological mechanisms and therapeutic approaches of autoimmune diseases, immunodeficiency, and cancer, and for the development of IL7R-targeted drugs.

 

Strain Strategy


Figure 1. Gene editing strategy of B6-hIL7R mice. The mouse Il7r endogenous extracellular domain (aa.21~239) was replaced with the human IL7R extracellular domain (aa.21~239). The murine IL7R signal peptide and cytoplasmic region (aa.1~20, aa.240~459) was preserved.

 

Application

  • IL7R-targeted drug screening, development, and evaluation;
  • Research on the pathological mechanisms and therapeutic approaches of autoimmune diseases, immunodeficiency, and cancer.

 

References
[1]Barata JT, Durum SK, Seddon B. Flip the coin: IL-7 and IL-7R in health and disease. Nat Immunol. 2019 Dec;20(12):1584-1593.
[2]Marković I, Savvides SN. Modulation of Signaling Mediated by TSLP and IL-7 in Inflammation, Autoimmune Diseases, and Cancer. Front Immunol. 2020 Jul 21;11:1557.
[3]Meyer A, Parmar PJ, Shahrara S. Significance of IL-7 and IL-7R in RA and autoimmunity. Autoimmun Rev. 2022 Jul;21(7):103120.
[4]Arango-Franco CA, Ogishi M, Unger S, Delmonte OM, Orrego JC, Yatim A, Velasquez-Lopera MM, Zea-Vera AF, Bohlen J, Chbihi M, Fayand A, Sánchez JP, Rojas J, Seeleuthner Y, Le Voyer T, Philippot Q, Payne KJ, Gervais A, Erazo-Borrás LV, Correa-Londoño LA, Cederholm A, Gallón-Duque A, Goncalves P, Doisne JM, Horev L, Charmeteau-de Muylder B, Álvarez JÁ, Arboleda DM, Pérez-Zapata L, Vásquez-Echeverri E, Moncada-Vélez M, López JA, Caicedo Y, Palterer B, Patiño PJ, Montoya CJ, Chaldebas M, Zhang P, Nguyen T, Ma CS, Jeljeli M, Alzate JF, Cabarcas F, Khan T, Rinchai D, Prétet JL, Boisson B; Generalized Verrucosis Japanese Consortium; Marr N, Ibrahim R, Molho-Pessach V, Boisson-Dupuis S, Kiritsi D, Barata JT, Landegren N, Neven B, Abel L, Lisco A, Béziat V, Jouanguy E, Bustamante J, Di Santo JP, Tangye SG, Notarangelo LD, Cheynier R, Natsuga K, Arias AA, Franco JL, Warnatz K, Casanova JL, Puel A. IL-7-dependent and -independent lineages of IL-7R-dependent human T cells. J Clin Invest. 2024 Oct 1;134(19):e180251.
[5]Wang C, Kong L, Kim S, Lee S, Oh S, Jo S, Jang I, Kim TD. The Role of IL-7 and IL-7R in Cancer Pathophysiology and Immunotherapy. Int J Mol Sci. 2022 Sep 8;23(18):10412.