B6-huIL12B Mouse

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].

B6-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 B6-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.