Interferons (IFNs) are potent cytokines that serve as a critical component of the body's first line of defense against viral infections, playing a key role in inflammation and immune control by directly inducing pathogen-inhibiting molecules that suppress viral replication ^[1]. Arthropod-borne viruses (arboviruses) like Dengue virus (DENV), Zika virus (ZIKV), and Yellow Fever virus (YFV) encode proteins that antagonize the IFN response, helping these viruses evade host immunity and maintain sufficient viral loads in the blood (viremia) to sustain the vector-host transmission. Arboviruses pose a significant public health threat, affecting around 3.9 billion people in tropical and subtropical regions. However, most preclinical studies suggest that arboviruses cannot inhibit IFN responses in mice, rendering immunocompetent mice resistant to infection, with low viral loads and limited circulation, thus limiting their use in infection research ^[2-3]. As a result, immunodeficient mouse models with defects in multiple IFN signaling pathways have become essential tools for studying arbovirus pathogenesis and vaccine development ^[2-4]. Studies have demonstrated that wild-type mice of strains like C57BL/6, CD-1, or 129 rarely exhibit clinical symptoms after infection with arboviruses such as ZIKV. However, the virus has been detected in the blood, ovaries, and spleen of ZIKV-infected 129 mice, suggesting that this strain may be more susceptible to arboviruses ^[5-6]. Because the virus can persist in the bloodstream without causing disease or death, the 129 strain can be used to evaluate the teratogenic effects of such viruses. Furthermore, the 129 strain is commonly used in interferon signaling-deficient models related to other viral infections ^[7-8]. The IFNAR1 gene encodes a protein that is an essential component of the type I interferon (IFN) receptor, playing a critical role in the antiviral and immune responses. IFNAR1 is primarily expressed in immune cells, such as lymphocytes and dendritic cells, and various tissues, including the liver, brain, and skin. Defects in IFNAR1, whether due to mutations or regulatory abnormalities, can lead to severe diseases such as systemic lupus erythematosus, where excessive immune activation results in tissue damage, and certain cancers. Other diseases associated with IFNAR1 include hepatitis C, yellow fever, measles, papilloma, and viral infections. The A129 (Ifnar1 KO) mice on a 129 background are a type I (α/β) interferon receptor (Ifnar1) gene knockout model. The absence of the IFNAR1 protein in these mice leads to a lack of type I IFN receptor function, thereby reducing immune response and increasing susceptibility to viral infections. Homozygous A129 (Ifnar1 KO) mice are viable and fertile, but they show increased susceptibility to arbovirus infections.

Interferons (IFNs) are potent cytokines that serve as a critical component of the body's first line of defense against viral infections, playing a key role in inflammation and immune control by directly inducing pathogen-inhibiting molecules that suppress viral replication ^[1]. Arthropod-borne viruses (arboviruses) like Dengue virus (DENV), Zika virus (ZIKV), and Yellow Fever virus (YFV) encode proteins that antagonize the IFN response, helping these viruses evade host immunity and maintain sufficient viral loads in the blood (viremia) to sustain the vector-host transmission. Arboviruses pose a significant public health threat, affecting around 3.9 billion people in tropical and subtropical regions. However, most preclinical studies suggest that arboviruses cannot inhibit IFN responses in mice, rendering immunocompetent mice resistant to infection, with low viral loads and limited circulation, thus limiting their use in infection research ^[2-3]. As a result, immunodeficient mouse models with defects in multiple IFN signaling pathways have become essential tools for studying arbovirus pathogenesis and vaccine development ^[2-4]. Studies have demonstrated that wild-type mice of strains like C57BL/6, CD-1, or 129 rarely exhibit clinical symptoms after infection with arboviruses such as ZIKV. However, the virus has been detected in the blood, ovaries, and spleen of ZIKV-infected 129 mice, suggesting that this strain may be more susceptible to arboviruses ^[5-6]. Because the virus can persist in the bloodstream without causing disease or death, the 129 strain can be used to evaluate the teratogenic effects of such viruses. Furthermore, the 129 strain is commonly used in interferon signaling-deficient models related to other viral infections ^[7-8]. The IFNAR1 gene encodes a key component of the type I IFN receptor, while the IFNGR1 gene encodes the ligand-binding chain (α) of the type II (γ) IFN receptor. AG129 mice, which are knockout models for both the type I (α/β) IFN receptor (Ifnar1) and the type II (γ) IFN receptor (Ifngr1), lack functional IFNAR1 and IFNGR1 proteins, resulting in deficiencies in α/β/γ interferon receptor signaling and heightened susceptibility to viral infections. Homozygous AG129 mice are viable and fertile, and exhibit increased sensitivity to arboviral infections, generating viremia similar to that seen in humans. Compared to IFNα/β/γR KO mice on the C57BL/6 background, the 129-background AG129 mice exhibit more pronounced neurological symptoms after infection ^[6,9].

Interleukin 17A (IL-17A) is a signature cytokine of the T helper 17 (Th17) subset of CD4+ T cells and one of the six members (IL-17A~IL-17F) of the IL-17 family. IL-17A is primarily produced by Th17 cells and can also be produced by other immune cells under certain conditions, including CD8+ T cells, γδT cells, natural killer T (NKT) cells, monocytes, neutrophils, and microglia ^[1]. IL-17A mediates downstream pathways that induce the production of inflammatory molecules, chemokines, antimicrobial peptides, and remodeling proteins, which have important effects on host defense, cell transport, immune regulation, and tissue repair, especially in inducing innate immune defense. In healthy skin, commensal microorganisms induce the production of IL-17A to provide antifungal protection. When the skin barrier is damaged, IL-17A promotes epithelial cell proliferation and can clear pathogenic factors, promoting tissue repair and wound healing ^[2]. IL-17A usually protects the body when it is acutely injured, but when a wound requires long-term healing and becomes a chronic injury, the role of IL-17A may transform into wound erosion or excessive proliferation, ultimately leading to loss of function ^[3]. IL-17A plays a key role in various infectious diseases, inflammations, autoimmune diseases, and cancers. Its high expression level is associated with chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, and multiple sclerosis. Lung injury caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely the result of the promotion of inflammatory reactions by cytokines such as IL-17A. Dysregulation of IL-17 signaling promotes pathogenic inflammation. IL-17A has a pathogenic role in mediating the important inflammatory pathway of psoriasis. The IL-23/Th17/IL-17A pathway is a key link in its pathogenesis, and inhibiting the expression of IL-17A can effectively alleviate psoriasis ^[4]. IL-17A is also associated with the course of ankylosing spondylitis (AS), and IL-17A inhibitors can effectively treat AS ^[5]. In addition, studies have shown that IL-17A is involved in the pathogenesis of neurodegenerative diseases in the central nervous system, and its expression level is related to the severity and progression of the disease ^[3]. The IL17F gene, located on chromosome 6p12.2, is primarily expressed by activated T cells, particularly Th17 cells, as well as other immune cells like γδ T cells and some innate immune cells ^[6]. The gene encodes the interleukin-17F (IL-17F) cytokine, a disulfide-linked homodimer protein that shares significant sequence homology with IL-17A ^[7]. Functionally, IL-17F is a pro-inflammatory cytokine that binds to the IL-17RA/RC receptor complex, triggering downstream signaling pathways involving Act1 and TRAF6, leading to the induction of various cytokines (like IL-6, IL-8, GM-CSF) and chemokines, which contribute to neutrophil recruitment and inflammation in barrier tissues such as the skin, lungs, and gut ^[8]. Elevated levels or dysregulation of IL-17F have been implicated in the pathogenesis of several autoimmune and inflammatory diseases, including psoriasis, rheumatoid arthritis, inflammatory bowel disease (like Crohn's disease and ulcerative colitis), and potentially Sjögren's syndrome, highlighting its role in chronic inflammatory processes ^[7-9]. The B6-huIL17A/huIL17F mouse is a dual-gene humanized model constructed by gene-editing technology. Based on the B6-hIL-17A mouse (catalog number: C001510), the sequences from the ATG start codon to the TGA stop codon of the endogenous mouse Il17f gene were replaced with the sequences from the ATG start codon to the TAA stop codon of the human IL17F gene. This model can be used for research on the pathogenesis of various chronic inflammatory diseases, such as rheumatoid arthritis (RA), psoriasis, multiple sclerosis, and inflammatory bowel diseases (IBD) and the related therapeutic drugs, as well as for the development of IL17A/IL17F-targeted drugs.

Interleukin 17A (IL-17A) is a signature cytokine of the T helper 17 (Th17) subset of CD4+ T cells and one of the six members (IL-17A~IL-17F) of the IL-17 family. IL-17A is primarily produced by Th17 cells and can also be produced by other immune cells under certain conditions, including CD8+ T cells, γδT cells, natural killer T (NKT) cells, monocytes, neutrophils, and microglia ^[1]. IL-17A mediates downstream pathways that induce the production of inflammatory molecules, chemokines, antimicrobial peptides, and remodeling proteins, which have important effects on host defense, cell transport, immune regulation, and tissue repair, especially in inducing innate immune defense. In healthy skin, commensal microorganisms induce the production of IL-17A to provide antifungal protection. When the skin barrier is damaged, IL-17A promotes epithelial cell proliferation and can clear pathogenic factors, promoting tissue repair and wound healing ^[2]. IL-17A usually protects the body when it is acutely injured, but when a wound requires long-term healing and becomes a chronic injury, the role of IL-17A may transform into wound erosion or excessive proliferation, ultimately leading to loss of function ^[3]. IL-17A plays a key role in various infectious diseases, inflammations, autoimmune diseases, and cancers. Its high expression level is associated with chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, and multiple sclerosis. Lung injury caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely the result of the promotion of inflammatory reactions by cytokines such as IL-17A. Dysregulation of IL-17 signaling promotes pathogenic inflammation. IL-17A has a pathogenic role in mediating the important inflammatory pathway of psoriasis. The IL-23/Th17/IL-17A pathway is a key link in its pathogenesis, and inhibiting the expression of IL-17A can effectively alleviate psoriasis ^[4]. IL-17A is also associated with the course of ankylosing spondylitis (AS), and IL-17A inhibitors can effectively treat AS ^[5]. In addition, studies have shown that IL-17A is involved in the pathogenesis of neurodegenerative diseases in the central nervous system, and its expression level is related to the severity and progression of the disease ^[3]. B6-hIL-17A mice are humanized mouse models that express human IL-17A protein. They were constructed by using gene editing technology to replace the sequence encoding the endogenous extracellular domain of the mouse Il17a gene with the corresponding sequence from the human IL17A gene while retaining the mouse signal peptide. This strain can be used for mechanism research and preclinical evaluation of therapeutic drugs for various chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, and multiple sclerosis. The homozygotes are viable and fertile.

TNF-like ligand 1A (TL1A), also known as TNF superfamily member 15 (TNFSF15), is a member of the tumor necrosis factor (TNF) family encoded by the TNFSF15 gene in humans. TL1A acts as a ligand for death receptor 3 (DR3) and decoy receptor 3 (DcR3), providing a stimulatory signal for downstream pathways. It regulates the proliferation, activation, and apoptosis of effector cells, as well as cytokine and chemokine production. TL1A is expressed in various immune cells, including monocytes, macrophages, dendritic cells, and T cells, as well as in non-immune cells such as synovial fibroblasts and endothelial cells. It plays a crucial role in modulating immune responses by promoting the differentiation and survival of T cells, particularly Th17 cells involved in inflammatory processes ^[1]. TL1A enhances IL-2 responses in anti-CD3/CD28-stimulated T cells and synergizes with IL-12 and IL-18 to augment IFN-γ release in human T and NK cells, biasing T cell differentiation toward a Th1 phenotype ^[2]. Dysregulation of TL1A expression is implicated in autoimmune diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), primary biliary cholangitis (PBC), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS) ^[1]. TL1A has emerged as a promising therapeutic target, with ongoing research focused on developing monoclonal antibodies and other biologics to neutralize TL1A and reduce inflammation in autoimmune disorders. Clinical trial results suggest that TL1A inhibition can be used in the treatment of various autoimmune diseases, particularly IBD ^[3-5]. The B6-hTL1A(TNFSF15) mouse is a humanized model constructed by replacing the mouse Tnfsf15 gene in situ with the human TNFSF15 gene using gene editing technology, in which the mouse Tnfsf15 endogenous extracellular domain will be replaced with the human TNFSF15 extracellular domain. The homozygous B6-hTL1A(TNFSF15) mice are viable and fertile, and can be used for studies on T cell differentiation and survival, immune response regulation, and pathogenesis of autoimmune diseases, as well as for TL1A-targeted drug development.

Neonatal Fc receptor (FcRn) is a cell surface receptor protein that binds to the Fc region of IgG antibodies. It is structurally similar to MHC class I molecules and comprises an α-chain and β2-microglobulin (β2M). The α-chain of the FcRn receptor is encoded by the Fcγ receptor and transporter (FCGRT) gene, while β2-microglobulin is encoded by the β-2-microglobulin (B2M) gene. FcRn is expressed widely on epithelial cells, endothelial cells, and hematopoietic cells, and is found in various tissues and organs, including the intestine, placenta, kidney, and liver ^[1-2]. IgG antibodies are the most abundant immunoglobulins in human serum (about 75%), and play an important role in the immune response by defending against pathogens and toxins. Compared to other immunoglobulins, IgG has a high circulating level, a longer half-life, and the ability to be transferred from mother to offspring. These properties are closely related to its interaction with FcRn. FcRn binds to the Fc region of IgG, preventing IgG molecules from being degraded by lysosomes. This prolongs the in vivo half-life of IgG and is involved in the transport, maintenance, and distribution metabolism of IgG. In addition, the specific transport process of IgG from the mother to the fetus to provide the fetus with short-term passive immunity is also mediated by FcRn ^[1-2]. In addition to its protective role, IgG autoantibodies are also associated with many pathological conditions. Therefore, novel FcRn blocking therapies are an effective strategy to reduce the circulating levels of pathogenic IgG autoantibodies and to reduce IgG-mediated diseases. In addition, many drugs also utilize FcRn's protective mechanism for IgG by fusing or conjugating with the Fc portion of IgG to prolong its serum half-life and improve its pharmacokinetics. The FCGRT gene encodes the α-chain of the FcRn protein, and its homologous genes are present in most mammals. This model is a humanized FcRn mouse, in which the sequence encoding the extracellular domain of the endogenous protein in the mouse Fcgrt gene has been replaced by the corresponding sequence in the human FCGRT gene. B6-hFcRn(Extra) mice are therefore useful for in vivo studies of IgG, screening of IgG antibody drug candidates, and evaluating the pharmacology, efficacy, and pharmacokinetics of drugs. The homozygous mice are viable and fertile.

The IL31RA gene encodes the interleukin-31 receptor subunit alpha, a type I cytokine receptor that serves as a critical mediator in neuroimmune communication. The protein typically functions as a heterodimer by associating with the oncostatin M receptor (OSMRβ) to form the functional IL-31 receptor complex, which triggers intracellular signaling through the JAK/STAT (primarily STAT3), PI3K/AKT, and MAPK pathways ^[1]. While the gene is expressed at low levels across various tissues, including the testis, thymus, and bone marrow, it is highly localized and functionally significant in CD14+ monocytes, macrophages, keratinocytes, and a specific subset of dorsal root ganglia (DRG) neurons. In these tissues, IL31RA plays a pivotal role in mediating pruritus (itching) and regulating skin immunity and inflammation ^[2]. Genetically, dysregulation of the IL31RA pathway is heavily implicated in the pathogenesis of inflammatory and pruritic diseases such as atopic dermatitis, prurigo nodularis, allergic asthma, and certain cutaneous T-cell lymphomas, making it a major therapeutic target for monoclonal antibodies like nemolizumab ^[3]. The B6-hIL31RA mouse is a humanized model constructed through gene-editing technology, in which the sequences from aa.19 to partial intron 4 of mouse Il31ra were deleted, and the human IL31RA extracellular domain-mouse Il31ra transmembrane-cytoplasmic domain-3’UTR of mouse Il31ra WPRE-BGH pA cassette was inserted downstream of mouse Il31ra signal peptide. This model can be used for research on inflammatory and pruritic diseases such as atopic dermatitis, prurigo nodularis, allergic asthma, and certain cutaneous T-cell lymphomas, as well as for screening, development, and preclinical evaluation of IL31RA-targeted therapeutics.

The TNFR2 gene, officially known as TNFRSF1B (Tumor Necrosis Factor Receptor Superfamily Member 1B), encodes the Tumor Necrosis Factor Receptor 2 protein (also called p75 or CD120b), a member of the TNF-receptor superfamily. Unlike its counterpart TNFR1 (which is widely expressed), TNFR2 exhibits more restricted expression, primarily on specific immune cells like regulatory T cells (Tregs), endothelial cells, and certain neuronal cells and microglia in the central nervous system (CNS), as well as on various cancer cells and mesenchymal stem cells ^[1]. The TNFR2 protein functions as a receptor for the cytokine TNF-α and generally signals for cell survival, proliferation, and anti-apoptosis by recruiting anti-apoptotic proteins and activating the NF-κB pathway (lacking the death domain found in TNFR1, which typically signals apoptosis) ^[2]. A soluble form of the receptor, sTNFR2, is also produced via proteolytic processing and can act as a TNF-α binding protein ^[3]. Dysregulation or polymorphisms of the TNFRSF1B gene and its encoded protein are associated with various diseases, including autoimmune disorders (such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease), several cancers (including breast, cervical, and colon cancer, where it promotes tumor growth and immune escape), and neurodegenerative diseases like Alzheimer's and schizophrenia. The B6-huTNFR2 (huTNFRSF1B) mouse is a humanized model constructed through gene-editing technology, in which the upstream of exon 2 to p.G258 of the mouse Tnfrsf1b gene was replaced with the upstream of exon 2 to p.D257 of the human TNFRSF1B gene. This model can be used for research on diseases such as autoimmune disorders, several cancers, neurodegenerative diseases like Alzheimer's and schizophrenia, as well as for screening, development, and preclinical evaluation of TNFRSF1B-targeted therapeutics.

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.

The B6-huIL4/huIL13/huTSLP mouse is a triple-gene humanized model obtained by mating B6-huIL4 mice (catalog number: C001628), B6-huIL13 mice (catalog number: C001634), and B6-huTSLP mice (catalog number: C001809). This model can be used for the mechanism research and development of treatment methods in allergic diseases, inflammation and autoimmune diseases, Th2 immune response, parasitic infections, tumor immunology, as well as the development of IL-4/IL13/TSLP-targeted drugs, and the pre-clinical evaluation of drug efficacy and safety.