Name: huIL12B Mouse
Brand: サイヤジェン（Cyagen）
SKU: C001619

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huIL12B Mouse

製品名

huIL12B Mouse

製品ID

C001619

系統名

C57BL/6NCya-Il12b^em1(hIL12B)/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、「huIL12B Mouse（カタログ番号C001619）はサイアジェンから購入しました。」と引用してください。

HUGO-GT Humanized Models

Tumor Target Humanized Mouse Models

Immune Target Humanized Mouse Models

Cytokine Gene Humanized Mouse Models

製品タイプ

年齢

遺伝子型

性別

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HUGO-GT Humanized Models

Tumor Target Humanized Mouse Models

Immune Target Humanized Mouse Models

Cytokine Gene Humanized Mouse Models

基本情報

検証 Data

系統詳細

The IL12B gene encodes the p40 subunit, a component of both interleukin-12 (IL-12) and IL-23, which are formed through heterodimerization with IL-12p35 and IL-23p19, respectively^[1]. Primarily secreted by activated monocytes, macrophages, dendritic cells, and B lymphocytes, these cytokines modulate Th1 and Th17 cell differentiation via the JAK-STAT signaling pathway, playing critical roles in immunity against intracellular pathogens and in inflammatory responses. IL-12 also enhances cellular immunity through the induction of interferon-gamma^[1-2]. IL12B gene expression is regulated by NF-κB and IRF transcription factors, and aberrant activation is implicated in autoimmune pathogenesis. Notably, single nucleotide polymorphisms (SNPs) within IL12B and an overactive IL-12/IL-23 pathway are strongly associated with susceptibility to autoimmune diseases^[1-3]. Monoclonal antibodies targeting IL-12B, such as ustekinumab, are clinically utilized for the treatment of moderate to severe psoriasis and Crohn's disease^[4-5]. Within the tumor microenvironment, IL-12B exhibits a complex functional profile, potentially enhancing cytotoxic T and NK cell activity, promoting IFN-γ production, and driving anti-tumor immunity. However, it can also contribute to tumor progression by fostering angiogenesis, depending on the tumor type and microenvironmental context^[6]. This duality underscores IL-12B as a key target for precise immunotherapy, particularly in combination therapies that simultaneously block IL-12 and IL-23 signaling, offering therapeutic potential across a spectrum of immune-related diseases and cancers^[1-6].

huIL12B mice are humanized models generated by gene editing technology, in which the entire base sequence of the mouse Il12b gene was replaced in situ with the corresponding sequence from the human IL12B gene. Homozygous huIL12B mice are viable and fertile. This model can be used to study the pathological mechanisms and therapeutic methods of immune-related diseases and cancer, as well as the screening and development of IL12B-targeted drugs, and preclinical efficacy and safety evaluations.

参考文献

Ullrich KA, Schulze LL, Paap EM, Müller TM, Neurath MF, Zundler S. Immunology of IL-12: An update on functional activities and implications for disease. EXCLI J. 2020 Dec 11;19:1563-1589.

Wu PB, Wu XM, Qian R, Hong C, Yitian G, Zhang G, Yu YJ. Association between IL12B polymorphisms and inflammatory bowel disease in Caucasian population: A meta-analysis. Cytokine. 2020 Dec;136:155296.

Manolova I, Ivanova M, Vasilev G, Stoilov R, Miteva L, Stanilova S. Impact of IL12B Polymorphisms on Genetic Susceptibility and IL-12p40 and IL-23 Serum Levels in Rheumatoid Arthritis. Immunol Invest. 2020 Feb;49(1-2):1-14.

Kocaaga A, Kocaaga M. Psoriasis: An Immunogenetic Perspective. Glob Med Genet. 2022 Jun 13;9(2):82-89.

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.

Zheng Y, Wang M, Tian T, Liu K, Liu X, Zhai Y, Lin S, Yang P, Li S, Dai Z, Lu J. Role of interleukin-12 gene polymorphisms in the onset risk of cancer: a meta-analysis. Oncotarget. 2017 May 2;8(18):29795-29807.

系統作製戦略

The sequences from the start codon to the stop codon of the endogenous mouse Il12b gene were replaced with the sequences from the start codon to the stop codon of the human IL12B gene.

Figure 1. Gene editing strategy of huIL12B mice.

適用分野

Screening, development, and preclinical efficacy evaluation of IL12B-targeted drugs;

Study of pathological mechanisms and therapeutic methods for immune-related diseases and cancer.

検証 Data

1. Gene Expression

RT-qPCR results showed that only murine Il12b mRNA was expressed in WT mice, while only human IL12B mRNA was expressed in the thymus and spleen of huIL12B mice. These results indicate that huIL12B mice successfully express human IL12B mRNA. (Bars represent mean ± SEM)

Figure 2. Gene expression in the thymus and spleen of huIL12B mice and wild-type (WT) mice (7-8 weeks old, homozygous, n=3). ND: Not detected.

2. Protein Expression (ELISA)

Mice were intraperitoneally injected with lipopolysaccharide (LPS) at a dose of 10 mg/kg for induction, with an induction duration of 2 hours. After induction, mouse plasma was collected to detect the expression levels of murine and human proteins, respectively. ELISA results showed that only Mouse IL12B p40 protein was expressed in the plasma of WT mice, and its expression level increased significantly after LPS induction. In contrast, only Human IL12 p40 protein was expressed in the plasma of huIL12B mice, with no detectable Mouse IL12B p40 protein; moreover, the expression level of this protein increased significantly after LPS induction, with no significant gender difference. These results confirm that huIL12B mice successfully express Human IL12 p40 protein in their plasma. (Bars represent mean ± SD)

Figure 3. Protein expression analysis in huIL12B mice and wild-type (WT) mice before and after LPS induction (6–7 weeks old, homozygous, n=3).

3. Ustekinumab PD Assessment

（1）Experimental Protocol and Group Design

Figure 4. Experimental protocol and group design for Ustekinumab efficacy evaluation. *Data provided by Cyagen Biosciences partners. *Ustekinumab is a fully human IgG1κ monoclonal antibody. It binds specifically to the shared p40 subunit of interleukin-12 (IL-12) and interleukin-23 (IL-23), thereby blocking downstream Th1 and Th17-mediated inflammatory responses. It is used to treat autoimmune diseases such as moderate-to-severe plaque psoriasis, psoriatic arthritis, and Crohn's disease. *Imiquimod (IMQ) is a small-molecule immunomodulator and a Toll-like receptor 7 (TLR7) agonist. It activates innate immune pathways to induce the local production of pro-inflammatory cytokines, such as interferon-α and tumor necrosis factor-α. Topical application of IMQ on the skin induces psoriasis-like inflammation in mice, characterized by erythema, scaling, and epidermal thickening, making it a common method for establishing psoriasis animal models.

（2）Total Psoriasis Score

Following the application of IMQ cream, huIL12B mice exhibited erythema, scaling, and significant skin thickening, with disease severity peaking on day 5. Throughout the study period, Ustekinumab treatment did not significantly reduce the total psoriasis score in huIL12B mice compared to the Group 2 (IMQ). (Data analyzed by one-way ANOVA and presented as mean ± SD.)

Figure 5. Effect of Ustekinumab on the total psoriasis score in an IMQ-induced psoriasis model in huIL12B mice (8-9 weeks old, female, homozygous, n=3). (A) Representative images of dorsal skin from each group; (B) The left panel shows the changes in total psoriasis scores over time, and the right panel compares the time-weighted area under the curve (AUC) of the total scores among groups. *Data provided by Cyagen Biosciences partners.

（3）Ear Swelling

Following the application of IMQ cream, the ears of huIL12B mice became thickened. Compared with Group G2 (IMQ), treatment with Ustekinumab 10mg/kg, s.c. Q7D×2 significantly reduced ear thickness in IMQ-induced huIL12B mice on days 5, 7, 10, and throughout the entire experimental period. Compared with Group G2 (IMQ), a single dose of Ustekinumab 10mg/kg, s.c. on day 5 significantly reduced ear swelling on day 7, but did not reduce ear thickness throughout the entire experimental period. At the experimental endpoint, both Ustekinumab treatment regimens significantly reduced ear swelling in IMQ-induced huIL12B mice compared to Group G2 (IMQ).

Figure 6. Effect of Ustekinumab on ear swelling in an IMQ-induced psoriasis model in huIL12B mice (8-9 weeks old, female, homozygous, n=3). (A) Time-course curves of ear thickness in each group; (B) Comparison of ear thickness among groups on days 5, 7, and 10. n=3, bars represent mean±SD, Two-way ANOVA, *P<0.05, **P<0.01, ****P<0.0001; (C) Comparison of the time-weighted area under the curve (AUC) of ear thickness among groups in Figure A. n=3, bars represent mean±SD, One-way ANOVA, ns indicates no statistical significance (P>0.05), **P<0.01，****P<0.0001; (D) Ear swelling at the experimental endpoint, calculated as the weight of the mouse ear treated with petroleum jelly or IMQ minus the weight of the untreated ear. n=3, bars represent mean±SD, One-way ANOVA, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. *Data provided by Cyagen Biosciences partners.

（4）Body Weight Change and Spleen Index

Ustekinumab had no significant effect on the body weight or spleen index of huIL12B mice after IMQ induction.

Figure 7. Effect of Ustekinumab on body weight and spleen index in IMQ-induced huIL12B mice (8-9 weeks old, female, homozygous, n=3). (A) Changes in body weight of mice in each group after induction with petroleum jelly or IMQ; (B) Comparison of spleen index among groups at the experimental endpoint. n=3, bars represent mean ± SD, one-way ANOVA, ***P<0.001. *Data provided by Cyagen Biosciences partners.

huIL12B Mouse

基本情報

検証 Data

関連リソース

遺伝子名

遺伝子別名

NCBI ID

染色体

MGI ID

さらに

データシート

系統詳細

参考文献

系統作製戦略

適用分野

1. Gene Expression

2. Protein Expression (ELISA)

3. Ustekinumab PD Assessment

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