B6-hIL13 Mice

Catalog Number: C001634

Strain Name: C57BL/6NCya-Il13em1(hIL13)/Cya

Genetic Background: C57BL/6NCya

Reproduction: Heterozygote x Heterozygote

 

Strain Description

Interleukin-13, encoded by the IL13 gene, is a key type 2 immune response cytokine, predominantly expressed by activated Th2 helper T cells, type 2 innate lymphoid cells (ILC2s), and mast cells, and central to type 2 immune responses elicited by allergens or other stimuli [1]. The IL-13 protein, a ~13 kDa molecule with a four-helix bundle structure, mediates its biological effects by binding to the cell surface receptor IL-13Rα1 and recruiting the IL-4Rα chain to form a functional receptor complex, thereby activating the downstream JAK/STAT6 signaling pathway [2]. Key functions of IL-13 include promoting B cell maturation and plasma cell differentiation, inducing IgE isotype switching, and suppressing the pro-inflammatory activity of macrophages, leading to reduced production of pro-inflammatory cytokines and chemokines [3]. Furthermore, IL-13 induces goblet cell hyperplasia, promotes mucus secretion, and contributes to airway remodeling and fibrosis [4]. Numerous studies have established the critical role of IL-13 in the pathogenesis of various diseases, including asthma, allergic rhinitis, atopic dermatitis, and eosinophilic esophagitis [1-4]. Consequently, targeting IL-13 and its signaling pathways has become a significant therapeutic strategy for these conditions; for example, the monoclonal antibody Dupilumab, which simultaneously blocks IL-4 and IL-13 signaling, has demonstrated substantial efficacy in treating diverse type 2 inflammation-related diseases [5]. Thus, IL-13 represents a promising therapeutic target for allergic and inflammatory disorders.

The B6-hIL13 mouse is a humanized model constructed using gene editing technology to replace the entire base sequence of the mouse Il13 gene in situ with the corresponding sequence from the human IL13 gene. This model can be used for studying the pathological mechanisms and therapeutic approaches of allergic and inflammatory diseases, and for the development of IL13-targeted drugs.

 

Strain Strategy


Figure 1. Gene editing strategy of B6-hIL13 mice. The sequences from ATG start codon to TAA stop codon of the endogenous mouse Il13 gene were replaced with the sequences from ATG start codon to TGA stop codon of the human IL13 gene.

 

Application

  • IL13-targeted drug screening, development, and evaluation;
  • Research on the pathological mechanisms and therapeutic approaches of allergic and inflammatory diseases.

 

References
[1]Dubin C, Del Duca E, Guttman-Yassky E. The IL-4, IL-13 and IL-31 pathways in atopic dermatitis. Expert Rev Clin Immunol. 2021 Aug;17(8):835-852.
[2]Iwaszko M, Biały S, Bogunia-Kubik K. Significance of Interleukin (IL)-4 and IL-13 in Inflammatory Arthritis. Cells. 2021 Nov 3;10(11):3000.
[3]Bernstein ZJ, Shenoy A, Chen A, Heller NM, Spangler JB. Engineering the IL-4/IL-13 axis for targeted immune modulation. Immunol Rev. 2023 Nov;320(1):29-57.
[4]Nur Husna SM, Md Shukri N, Mohd Ashari NS, Wong KK. IL-4/IL-13 axis as therapeutic targets in allergic rhinitis and asthma. PeerJ. 2022 May 30;10:e13444.
[5]Le Floc'h A, Allinne J, Nagashima K, Scott G, Birchard D, Asrat S, Bai Y, Lim WK, Martin J, Huang T, Potocky TB, Kim JH, Rafique A, Papadopoulos NJ, Stahl N, Yancopoulos GD, Murphy AJ, Sleeman MA, Orengo JM. Dual blockade of IL-4 and IL-13 with dupilumab, an IL-4Rα antibody, is required to broadly inhibit type 2 inflammation. Allergy. 2020 May;75(5):1188-1204.