Cystic Fibrosis (CF) is an autosomal recessive disorder causing severe damage to the lungs, digestive system, and other organs. It thickens mucus, sweat, and digestive fluids, blocking ducts and channels. The disease manifests as a persistent cough, hyperinflation of lung lobes, chronic nasal congestion, headaches, sleep disorders, digestive and reproductive system disorders, and nutritional and growth development disorders. CF is caused by mutations in the CF-transmembrane conductance regulator (CFTR) gene, which encodes a cAMP-dependent chloride ion channel protein. Abnormal CFTR function can cause transmembrane transport disorders of chloride ions and bicarbonate, leading to mucus obstruction in exocrine glands, and affecting respiration, digestion, endocrine, and reproduction^[1-2]. Current CF treatment research primarily focuses on small-molecule drugs, but gene therapy-related pipelines are emerging. Eluforsen, a Phase 1 ASO-related pipeline by ProQR, targets the F508dcl mutation region of the CFTR gene to restore its function^[3-4]. Most gene therapies act on the human CFTR gene, and humanizing mouse genes could expedite these treatments into clinical stages, emphasizing precision in therapeutic development. This strain is a mouse Cftr gene humanized model and can be used for research on CF. The homozygous B6-hCFTR mice are viable and fertile. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen can also generate hot mutation models based on this strain and provide customized services for specific mutations to meet the experimental needs in pharmacology and other fields.

The CLEC4C gene, also known as BDCA-2 or CD303, encodes a type II transmembrane C-type lectin receptor predominantly expressed by plasmacytoid dendritic cells (pDCs) ^[1]. This receptor plays a critical role in pDC biology and serves as a key marker for this cell type ^[2]. The CLEC4C protein, featuring a carbohydrate recognition domain, is implicated in the capture and subsequent processing of antigens, potentially through the recognition of specific glycans and immunoglobulin G ^[1]. Functionally, CLEC4C acts as a signaling receptor within pDCs, and its engagement can negatively regulate the production of type I interferons, thereby modulating immune responses ^[2]. Notably, dysregulation of CLEC4C expression and pDC function has been associated with the pathogenesis of autoimmune disorders, including systemic lupus erythematosus (SLE), as well as in the context of certain hematological malignancies ^[3]. Litifilimab is a monoclonal antibody that targets CLEC4C and is under investigation for the treatment of SLE and other interferonopathies ^[4]. CLEC4C is a human gene, while Clec4b1 is its orthologous gene in mice. The B6-hCLEC4C mouse is a humanized model constructed by replacing the mouse Clec4b1 endogenous extracellular domain with the human CLEC4C extracellular domain. This model can be used to study the pathological mechanisms and therapeutic methods of autoimmune disorders and hematological malignancies, as well as the screening and development of CLEC4C-targeted drugs, and preclinical efficacy and safety evaluations.

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 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. 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 ^[6-7]. 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 ^[6-7]. 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 ^[8]. 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 ^[6-9]. B6-hIL13/hIL23A mice are humanized models generated by crossing B6-hIL13 mice (Product No.: C001634) with B6-hIL23A mice (Product No.: C001618). These mice are suitable for studying the pathological mechanisms and therapeutic strategies of allergic and inflammatory diseases, immune-related disorders, and cancer, as well as for the screening, development, and preclinical evaluation of IL13/IL23A-targeted drugs.

Thymic stromal lymphopoietin (TSLP), an interleukin-7 (IL-7) family cytokine, is encoded by the TSLP gene and is predominantly produced by epithelial cells. Its expression is notably upregulated by environmental cues, including allergens and proteases, positioning it as a sentinel at the interface of environmental exposure and immune activation ^[1-2]. Secreted by a range of cell types, such as epithelial cells, keratinocytes, mast cells, and dendritic cells, TSLP is critical in the initiation of immune responses, primarily through the activation of dendritic cells and subsequent polarization of T helper type 2 (Th2) cell differentiation. This process has broad implications for diverse immune cell populations and B cell functions relevant to allergic inflammation ^[2]. Transcriptional regulation of TSLP gene expression is tightly controlled by factors including NF-κB and AP-1, with genetic polymorphisms within the TSLP locus being strongly implicated in asthma susceptibility ^[1-3]. Dysregulated TSLP signaling is now recognized as a pivotal factor in the pathogenesis of atopic disorders, encompassing conditions such as atopic dermatitis, asthma, allergic rhinitis, and eosinophilic esophagitis ^[1-4]. For example, tezepelumab, a monoclonal antibody that blocks the TSLP signaling pathway, has demonstrated significant efficacy in clinical trials for patients with severe asthma, reducing acute exacerbations and improving lung function ^[4]. Consequently, TSLP is under intense investigation as a therapeutic target, with current strategies focusing on disrupting its signaling pathways to modulate allergic and inflammatory diseases ^[5]. The B6-hTSLP mouse is a humanized model constructed using gene editing technology, where the mouse Tslp endogenous domain was replaced with the human TSLP domain . The murine signal peptide was preserved. This model can be used for studying the pathological mechanisms and therapeutic approaches of allergic and inflammatory diseases and for the development of TSLP-targeted drugs.

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 is composed of 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. The ALB gene encodes albumin, mainly produced in the liver, and is the most abundant protein in human plasma, accounting for 60% to 65% of total plasma protein. The proprotein encoded by ALB is processed to produce a functional protein, and the EPI-X4 peptide derived from this protein is an endogenous inhibitor of the CXCR4 chemokine receptor. Albumin plays a role in regulating plasma colloid osmotic pressure, helping to maintain blood circulation and isolating and transporting many metabolites within the body, especially insoluble hydrophobic metabolites ^[3]. Human Serum Albumin (HSA) is an important carrier protein involved in the transport of a variety of endogenous molecules, including hormones, fatty acids, and metabolic products, as well as exogenous drugs. As a natural carrier protein, HSA has multiple ligand binding sites and a plasma half-life of up to 19 days, making it a promising drug carrier. Several HSA-based drug delivery systems have been approved for clinical trials ^[4-5]. Albumin is also the primary transporter of zinc, calcium, and magnesium in plasma, binding approximately 80% of all plasma zinc and about 45% of circulating calcium and magnesium, with an affinity ranking order of zinc > calcium > magnesium. Additionally, albumin exhibits broad substrate-specific esterase-like activity, with enzymatic properties. It can also bind to the bacterial siderophore enterobactin, inhibiting enterobactin-mediated uptake of iron from transferrin by Escherichia coli, thus limiting iron availability and intestinal bacterial growth ^[6]. Diseases related to the ALB gene include hyperthyroxinemia, familial dysalbuminemic hyperthyroxinemia, and analbuminemia ^[7]. The B6-hFcRn (Extra) /hALB (HSA) mice were obtained by crossbreeding B6N-hFCRN (Extra) humanized mice (Catalog Number: C001701) with B6-hALB (HSA) humanized mice (Catalog Number: C001492). In this model, the gene sequence encoding the extracellular domain of the FCRN protein in the mouse Fcgrt gene was replaced with the corresponding gene sequence from the human FCGRT gene, which is the binding site for the FCRN and IgG antibody Fc structure. Additionally, the mouse Alb gene sequence (including UTR regions) was replaced in situ with the human ALB gene sequence. Therefore, the B6-hFcRn (Extra) /hALB (HSA) mice can be used for in vivo studies of human IgG antibodies, drug development using human serum albumin (HSA) as a carrier, as well as for pharmacodynamic and pharmacokinetic studies.

The TNFRSF17 gene, also known as BCMA, encodes a protein belonging to the tumor necrosis factor receptor superfamily. This protein is predominantly expressed in mature B lymphocytes, particularly plasma cells, with lower expression in early B cells and non-B cells ^[1-2]. As a type III transmembrane glycoprotein, TNFRSF17 plays a critical role in B cell survival and differentiation, acting as a key regulator of B cell maturation ^[2]. Functionally, TNFRSF17 primarily acts as a receptor for the B cell-activating factor (BAFF). Upon BAFF binding, it activates both the classical NF-κB pathway and the non-classical MAPK8/JNK pathway, subsequently regulating downstream gene expression to promote B cell survival, proliferation, and antibody secretion. Furthermore, TNFRSF17 can interact with TNFR-associated factors (TRAFs) 1, 2, and 3, further mediating physiological processes related to cell differentiation and growth ^[1-2]. Multiple studies have demonstrated that the TNFRSF17 gene and its protein are associated with various B cell-related diseases. Notably, this gene exhibits abnormally high expression in diseases such as multiple myeloma and systemic lupus erythematosus, rendering it a potential therapeutic target for these conditions ^[3-4]. The B6-hBCMA (TNFRSF17) mouse is a humanized model constructed using gene editing technology, where the mouse BCMA endogenous extracellular domain was replaced with the human BCMA extracellular domain. Homozygous B6-hBCMA (TNFRSF17) mice are viable and fertile. This model can be used for studying the pathological mechanisms and therapeutic approaches of multiple myeloma, systemic lupus erythematosus, and various B cell-related diseases and for the development of BCMA-targeted drugs.

Interleukin-4 (IL-4) and its receptor, IL-4R, are pivotal regulators of immune responses and inflammation. The IL4 gene encodes the IL-4 cytokine, a multifunctional protein predominantly secreted by Th2 cells, mast cells, and eosinophils, while the IL4R gene encodes the IL-4 receptor, which is expressed on a variety of immune cells, including B cells, T cells, macrophages, and endothelial cells. IL-4 binds to IL-4R, which exists in two distinct forms: Type I (comprising IL-4Rα and the common γ-chain) and Type II (comprising IL-4Rα and IL-13Rα1) ^[1]. This interaction activates the JAK-STAT signaling pathway, driving Th2 cell differentiation, B cell class switching to IgE, and anti-inflammatory responses. The IL-4/IL-4R signaling axis is critically implicated in allergic diseases such as asthma, atopic dermatitis, and allergic rhinitis, as well as in parasitic infections and certain cancers ^[2-5]. Dysregulation of this pathway underlies various pathological conditions, positioning IL-4R as a promising therapeutic target. For instance, dupilumab, a monoclonal antibody targeting IL-4Rα, has been approved for the treatment of atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyps, underscoring the therapeutic potential of modulating this pathway ^[6-7]. B6-hIL4RA mice are humanized models generated using gene editing technology by replacing the extracellular domain of the mouse Il4ra with the corresponding human IL4R extracellular domain, while retaining the murine signal peptide. Homozygous B6-hIL4RA mice are viable and fertile. This model is an invaluable tool for studying allergic diseases (e.g., asthma and atopic dermatitis), Th2 immune responses, parasitic infections, tumor immunology, and chronic inflammation. Furthermore, it is a robust preclinical platform for evaluating the efficacy and mechanisms of therapeutic agents targeting the IL-4Rα.

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 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 ^[6-7]. 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 ^[6-7]. 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 ^[8]. 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 ^[6-9]. B6-hTL1A/hIL23A mice are humanized models generated by crossing B6-hTL1A (TNFSF15) mice (Catalog No.: C001603) with B6-hIL23A mice (Catalog No.: C001618). These mice are suitable for studying the pathological mechanisms and therapeutic strategies of allergic and inflammatory diseases, immune-related disorders, and cancer, as well as for the screening, development, and preclinical evaluation of TL1A/IL23A-targeted drugs.

Interleukin-4 (IL-4) and its receptor, IL-4R, are pivotal regulators of immune responses and inflammation. The IL4 gene encodes the IL-4 cytokine, a multifunctional protein predominantly secreted by Th2 cells, mast cells, and eosinophils, while the IL4R gene encodes the IL-4 receptor, which is expressed on a variety of immune cells, including B cells, T cells, macrophages, and endothelial cells. IL-4 binds to IL-4R, which exists in two distinct forms: Type I (comprising IL-4Rα and the common γ-chain) and Type II (comprising IL-4Rα and IL-13Rα1) ^[1]. This interaction activates the JAK-STAT signaling pathway, driving Th2 cell differentiation, B cell class switching to IgE, and anti-inflammatory responses. The IL-4/IL-4R signaling axis is critically implicated in allergic diseases such as asthma, atopic dermatitis, and allergic rhinitis, as well as in parasitic infections and certain cancers ^[2-5]. Dysregulation of this pathway underlies various pathological conditions, positioning IL-4R as a promising therapeutic target. For instance, dupilumab, a monoclonal antibody targeting IL-4Rα, has been approved for the treatment of atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyps, underscoring the therapeutic potential of modulating this pathway ^[6-7]. The B6-hIL4/hIL4RA mouse model is generated by crossing IL4 humanized mice (Catalog Number: C001628) with IL4R humanized mice (Catalog Number: C001629), resulting in a dual-humanized model. This model faithfully recapitulates the human IL-4/IL-4R signaling pathway, making it an invaluable tool for studying allergic diseases (e.g., asthma and atopic dermatitis), Th2 immune responses, parasitic infections, tumor immunology, and chronic inflammation. Furthermore, it serves as a robust preclinical platform for evaluating the efficacy and mechanisms of therapeutic agents targeting the IL-4/IL-4Rα pathway.

Epidermolysis bullosa (EB) is a hereditary skin disease characterized by the formation of blisters and bullae on the skin and mucous membranes after minor trauma or friction. Common clinical symptoms include blisters, blood blisters, and erosion on the skin. According to the different sites of onset, hereditary EB can be divided into three types: Epidermolysis Bullosa Simplex (EBS), Junctional Epidermolysis Bullosa (JEB), and Dystrophic Epidermolysis Bullosa (DEB). Mutations in the COL7A1 gene cause Dystrophic Epidermolysis Bullosa (DEB), and the different clinical phenotypes presented by DEB are related to the mutation sites and forms of the COL7A1 gene. The COL7A1 gene encodes type VII collagen, which forms anchoring fibrils that bind dermal tissue to epidermal tissue. Functional anchoring fibril deficiency caused by COL7A1 mutations makes the patient’s skin extremely fragile and easily blistered or torn due to minor friction or trauma. At present, 324 pathogenic mutations of the COL7A1 gene related to DEB have been found, including nonsense, missense, deletion, insertion, splicing, and regulation ^[1]. The current DEB treatment pipeline is mainly based on gene therapy and small nucleic acid drugs, including ASO drugs, siRNA drugs, and gene therapy based on CRISPR and AAV vector delivery. Among them, COL7A1 is the most important therapeutic target. B-Vec, developed by Krystal Biotech delivers functional COL7A1 genes to skin cells of DEB patients with COL7A1 mutations through HSV-1 vectors to produce functional proteins to promote wound healing and was the first approved gene therapy drug for the DEB ^[2-5]. In addition, since most ASO, siRNA, and CRISPR-based therapies target human COL7A1 genes, considering the genetic differences between animals and humans, humanizing mouse genes will help promote further clinical translation of therapies targeting COL7A1. This strain is a mouse Col7a1 gene humanized model and can be used for research on DEB. The homozygous B6-hCOL7A1 mice are viable and fertile ^[6-7]. Leveraging its proprietary TurboKnockout fusion BAC recombination technology, Cyagen can also generate hot mutation models based on this strain and provide customized services for specific mutations to meet the experimental needs in pharmacology and other fields related to EB.