B6-hIL23A&hIL12B Mice

Catalog Number: C001620

Strain Name: C57BL/6NCya-Il23aem1(hIL23A)Il12bem1(hIL12B)/Cya

Genetic Background: C57BL/6NCya

Reproduction: Homozygote B6-IL12B mice x Heterozygote B6-hIL23A mice

 

Strain Description

The IL23A gene encodes the p19 subunit, a component of interleukin-23 (IL-23), which forms a heterodimer with the p40 subunit (encoded by IL12B) to generate the functional IL-23 cytokine [1]. Primarily expressed by activated dendritic cells, macrophages, and monocytes, IL-23 signals through the IL-23 receptor (IL-23R) complex, activating the JAK-STAT pathway to promote Th17 cell differentiation and maintain IL-17 production. This process drives inflammatory responses and mucosal immunity against extracellular pathogens [1-2]. Genetic polymorphisms within IL23A are strongly associated with autoimmune and inflammatory diseases, including psoriasis, Crohn's disease, and inflammatory bowel disease, due to dysregulated Th17 activity and chronic inflammation [1-2]. Monoclonal antibodies targeting IL-23, such as risankizumab and guselkumab, selectively block the p19 subunit, demonstrating therapeutic efficacy in psoriasis and inflammatory bowel diseases by suppressing pathogenic IL-17/Th17 pathways [3]. Also, monoclonal antibodies targeting IL-12B, such as ustekinumab, are clinically utilized for the treatment of moderate to severe psoriasis and Crohn's disease [5]. While IL-23 plays a role in protective immunity, its overactivation contributes to tissue damage in autoimmune settings, highlighting its dual function in immune regulation and disease pathogenesis [1-4].

B6-hIL23A&hIL12B mice are IL12B and IL23A double humanized mouse models obtained by mating IL12B humanized mouse models with IL23A humanized mouse models. They express human IL12B and IL23A genomic sequences under the control of mouse promoters. This model is capable of reproducing human IL-23 cytokines and is a valuable tool for studying immune-related diseases. In addition, this model also provides a powerful preclinical research platform for evaluating the efficacy and mechanism of therapeutic drugs targeting IL-23 cytokines.

 

Strain Strategy


Figure 1. Gene Editing Strategy for B6-hIL23A Mice. The mouse Il23a gene sequence encoding the protein (aa. 22-196) was replaced in situ with the corresponding human IL23A sequence (aa. 20-189), while retaining the sequence encoding the mouse endogenous signal peptide (aa. 1-21).


Figure 2. Gene editing strategy of B6-hIL12B mice. The sequences from ATG start codon to TAG stop codon of the endogenous mouse Il12b gene were replaced with the sequences from ATG start codon to TAG stop codon of the human IL12B gene.

 

Application

  • IL23A/IL12B-targeted drug screening, development, and evaluation;
  • Research on the pathological mechanisms and therapeutic approaches of immune-related diseases.

 

References
[1]Schinocca C, Rizzo C, Fasano S, Grasso G, La Barbera L, Ciccia F, Guggino G. Role of the IL-23/IL-17 Pathway in Rheumatic Diseases: An Overview. Front Immunol. 2021 Feb 22;12:637829. doi: 10.3389/fimmu.2021.637829. PMID: 33692806; PMCID: PMC7937623.
[2]Jairath V, Acosta Felquer ML, Cho RJ. IL-23 inhibition for chronic inflammatory disease. Lancet. 2024 Oct 26;404(10463):1679-1692. doi: 10.1016/S0140-6736(24)01750-1. Erratum in: Lancet. 2025 Dec 21;404(10471):2542.
[3]Huang YW, Tsai TF. A drug safety evaluation of risankizumab for psoriasis. Expert Opin Drug Saf. 2020 Apr;19(4):395-402.
[4]Sun C, Xia J. Treatment of psoriasis: janus kinases inhibitors and biologics for the interleukin-23/Th17 axis. Minerva Med. 2020 Jun;111(3):254-265.
[5]Benson JM, Peritt D, Scallon BJ, Heavner GA, Shealy DJ, Giles-Komar JM, Mascelli MA. Discovery and mechanism of ustekinumab: a human monoclonal antibody targeting interleukin-12 and interleukin-23 for treatment of immune-mediated disorders. MAbs. 2011 Nov-Dec;3(6):535-45.