The CD19 gene encodes a member of the immunoglobulin gene superfamily. As a key co-receptor in the B cell receptor (BCR) signaling pathway, it is crucial for B cell development, activation, and differentiation. CD19, a pan-B-cell marker exclusively expressed in the B cell lineage, remains stable throughout B cell development, from pro-B cells to mature and memory B cells. It acts as a positive regulator of BCR signal transduction by forming a B cell-specific signaling complex with CD21 (complement receptor 2), CD81 (tetraspanin), and CD225 (Leu13), which lowers the threshold for antigen-induced B cell activation ^[1]. Dysregulation of CD19 is strongly linked to autoimmune diseases such as systemic lupus erythematosus (SLE) and B cell malignancies like acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma. Mutations in this gene are associated with common variable immunodeficiency 3 (CVID3), characterized by impaired B cell differentiation and hypogammaglobulinemia. Owing to its B cell-specific expression, CD19 has become a pivotal target for immunotherapy. For example, anti-CD19 CAR-T cell therapy (e.g., Tisagenlecleucel) has shown remarkable efficacy in refractory or relapsed ALL ^[2]. Recent studies have also explored CD19-targeted bispecific antibodies (e.g., blinatumomab) to enhance tumor cell clearance ^[3]. B6-hCD19 mice are a humanized model generated by replacing the mouse endogenous Cd19 gene sequence from the ATG start codon to part of intron 4 with the corresponding human CD19 gene sequence using gene editing technology. This model is applicable for studying B cell development and function, as well as therapeutic research on autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), and B cell malignancies. It is an ideal research platform for preclinical efficacy evaluation of anti-human CD19 CAR-T cell therapy, and the development of bispecific antibodies and combination therapies.

The TNFRSF13B gene encodes the transmembrane activator and CAML interactor (TACI), a receptor belonging to the tumor necrosis factor receptor superfamily, predominantly expressed on B lymphocytes. TACI plays a critical role in humoral immunity by recognizing the TNF ligands B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) ^[1]. Upon ligand binding, TACI modulates intracellular signaling pathways, including NFAT, AP1, and NF-κB, which are essential for B cell survival, maturation into plasma cells, and the production of immunoglobulins ^[2]. Notably, TNFRSF13B is highly polymorphic, and specific genetic variants are strongly associated with the pathogenesis of common variable immunodeficiency (CVID), a primary immunodeficiency characterized by hypogammaglobulinemia and increased susceptibility to infection ^[3]. While the precise mechanisms by which these variants contribute to disease are still under investigation, they often result in impaired TACI function, disrupting normal B cell development and antibody responses ^[4]. Further research into the regulation and function of TACI is crucial for understanding the complex etiology of CVID and for developing targeted therapeutic strategies for this and potentially other immune-related disorders. The B6-hTNFRSF13B mouse is a humanized model constructed by replacing the exon 2 plus partial intron 2 of the mouse Tnfrsf13b gene in situ with the "Kozak-TNFRSF13B chimeric CDS-3'UTR of mouse Tnfrsf13b-WPRE-BGH pA" cassette. The B6-hTNFRSF13B mice can be used for studies on common variable immunodeficiency (CVID), and pathogenesis of immune-related diseases, as well as for TNFRSF13B-targeted drug development.

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.

The gene TNFRSF13C encodes the B cell-activating factor receptor (BAFF-R), also known as BLyS receptor 3 (BR3) or CD268. As a member of the tumor necrosis factor receptor superfamily (TNFRSF), BAFF-R functions as a crucial type III transmembrane signaling protein on lymphocytes. Its expression is predominantly observed on the surface of B cells throughout various stages of their development, from transitional to mature naive and memory populations, underscoring its vital role in peripheral B cell homeostasis ^[1]. BAFF-R serves as the primary receptor for the cytokine BAFF (TNFSF13B), and their interaction delivers essential survival and maturation signals to B cells, mediated through downstream pathways including the activation of NF-κB and PI3K. Genetic alterations in TNFRSF13C, including point mutations and deletions, or dysregulation of the BAFF-BAFF-R axis, are increasingly recognized for their contribution to immune pathology ^[2]. Such aberrations are associated with primary immunodeficiencies like common variable immunodeficiency (CVID), characterized by profound defects in antibody production and recurrent infections, as well as a range of autoimmune diseases such as systemic lupus erythematosus (SLE) and Sjögren's syndrome, and certain B cell malignancies ^[2-3]. The critical, non-redundant function of BAFF-R in B cell biology highlights its significance as a key node in adaptive immunity and positions the BAFF-BAFF-R pathway as a compelling target for therapeutic intervention in a spectrum of immune-mediated disorders. The B6-hBAFFR (hTNFRSF13C) mouse is a humanized model constructed by replacing the sequence of the mouse Tnfrsf13c endogenous extracellular domain in situ with the corresponding extracellular domain from the human TNFRSF13C. The B6-hBAFFR (hTNFRSF13C) mice can be used for the study of the pathogenesis of immune-mediated disorders such as common variable immunodeficiency (CVID), systemic lupus erythematosus (SLE), and Sjögren's syndrome, and certain B cell malignancies, as well as for TNFRSF13C-targeted drug development.

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.

Cluster of Differentiation 3 (CD3) is a protein complex that acts as a co-receptor for T cells and is involved in the activation of cytotoxic T cells (CTLs) and helper T cells (THs). CD3 consists of five polypeptide chains: γ, δ, ε, ζ, and η, all of which are transmembrane proteins. The transmembrane regions of CD3 molecules connect with the transmembrane regions of TCR's two polypeptide chains through salt bridges, forming the TCR-CD3 complex, which is essential for T cell antigen recognition ^[1-2]. After TCR recognizes an antigen, the activation signal is transduced by CD3 into the T cell. CD3 is highly specific at all developmental stages of T cells, thus it is considered a T cell-specific immunohistochemical marker. Additionally, CD3 is present in almost all T cell lymphomas and leukemias and can be used to distinguish between morphologically similar B cell and bone marrow tumors. Due to its significant role in T cell activation and antigen recognition, CD3 is an important drug target in immunosuppressive therapy for type 1 diabetes and other autoimmune diseases ^[3]. The EPCAM gene encodes a transmembrane glycoprotein, Epithelial Cell Adhesion Molecule (EPCAM), also known as CD326 or Trop-1, which mediates calcium-independent homotypic cell adhesion and participates in fundamental processes including cell adhesion, migration, proliferation, and signal transduction, thereby maintaining epithelial tissue integrity ^[4]. While normally expressed on the surface of epithelial cells in organs such as the gastrointestinal tract, lungs, and skin, EPCAM is frequently overexpressed in various cancers, including colorectal, breast, and pancreatic carcinomas, but is largely absent or weakly expressed in healthy squamous epithelia ^[4]. Structurally, EPCAM comprises an extracellular domain (EpEX) mediating intercellular adhesion, a transmembrane domain, and a short intracellular domain (EpICD). Upon proteolytic cleavage by ADAM17 and γ-secretase, EpICD translocates to the nucleus, activating oncogenic pathways such as Wnt/β-catenin, ERK, and FAK-AKT, which promotes epithelial-mesenchymal transition (EMT), tumor progression, and metastasis ^[5]. Notably, EPCAM serves as a marker for circulating tumor cells (CTCs) and cancer stem cells, and its downregulation during EMT can complicate advanced cancer detection ^[5-6]. Furthermore, dysregulated EPCAM expression is associated with congenital tufting enteropathy (CTE), a severe intestinal epithelial dysfunction ^[5]. Given its involvement in tumor metastasis through interaction with HGFR (c-Met), targeting EPCAM with strategies like the neutralizing antibody EpAb2-6 in combination with HGFR inhibitors has shown promising preclinical efficacy ^[7]. The B6-hCD3/hEPCAM mouse is obtained by crossbreeding B6-hCD3 mice (Catalog No.: C001325) with B6-hEPCAM mice. It can be used for the development of CD3/EPCAM-targeted drugs, as well as for research in tumor immunotherapy and autoimmune disease-related drugs.

The CRBN gene, located on chromosome 3, exhibits broad expression across diverse tissues, including the brain, kidney, muscle, and immune cell populations such as monocytes, macrophages, dendritic cells, and B lymphocytes ^[1]. This gene encodes cereblon, a protein that functions as a key substrate receptor within the CRL4-CRBN E3 ubiquitin ligase complex. This complex mediates the ubiquitination and subsequent proteasomal degradation of specific target proteins, thereby regulating crucial cellular processes encompassing protein homeostasis, ion transport, and AMPK signaling ^[1-2]. Notably, mutations in CRBN are implicated in autosomal recessive nonsyndromic intellectual disability ^[2]. Furthermore, Cereblon protein serves as a primary molecular target for targeted protein degradation (TBD) therapy by specifically modulating the enzymatic activity of the CRL4-CRBN complex and altering its substrate recognition properties, thereby enabling the selective degradation of specific transcription factors. This molecular mechanism has emerged as a critical theoretical foundation for the clinical treatment of malignant hematological malignancies such as multiple myeloma, leading to the development of diverse therapeutic modalities including molecular glues and proteolysis targeting chimeras (PROTACs) ^[3-5]. B6-hCRBN mice are humanized models generated by gene editing technology, in which the exon 2 to partial intron 2 of the mouse Crbn gene was replaced in situ with the Exon 2~11 of the coding sequence (CDS) of human CRBN gene. This model can be used to study the pathological mechanisms and therapeutic methods of autosomal recessive nonsyndromic intellectual disability and multiple myeloma and other hematological cancers, as well as the screening, development, and preclinical efficacy and safety evaluation of CRBN-based targeted protein degradation (TBD) therapies.

The CRBN gene, located on chromosome 3, exhibits broad expression across diverse tissues, including the brain, kidney, muscle, and immune cell populations such as monocytes, macrophages, dendritic cells, and B lymphocytes ^[1]. This gene encodes cereblon, a protein that functions as a key substrate receptor within the CRL4-CRBN E3 ubiquitin ligase complex. This complex mediates the ubiquitination and subsequent proteasomal degradation of specific target proteins, thereby regulating crucial cellular processes encompassing protein homeostasis, ion transport, and AMPK signaling ^[1-2]. Notably, mutations in CRBN are implicated in autosomal recessive nonsyndromic intellectual disability ^[2]. Furthermore, Cereblon protein serves as a primary molecular target for targeted protein degradation (TBD) therapy by specifically modulating the enzymatic activity of the CRL4-CRBN complex and altering its substrate recognition properties, thereby enabling the selective degradation of specific transcription factors. This molecular mechanism has emerged as a critical theoretical foundation for the clinical treatment of malignant hematological malignancies such as multiple myeloma, leading to the development of diverse therapeutic modalities including molecular glues and proteolysis targeting chimeras (PROTACs) ^[3-5]. BALB/c-hCRBN mice are humanized models generated by gene editing technology, in which the exon 2 to partial intron 2 of the mouse Crbn gene was replaced in situ with the Exon 2~11 of the coding sequence (CDS) of human CRBN gene. This model can be used to study the pathological mechanisms and therapeutic methods of autosomal recessive nonsyndromic intellectual disability and multiple myeloma and other hematological cancers, as well as the screening, development, and preclinical efficacy and safety evaluation of CRBN-based targeted protein degradation (TBD) therapies.

CD47, also known as Integrin Associated Protein (IAP), is a transmembrane protein that belongs to the immunoglobulin superfamily. It is widely expressed on the surface of almost all normal cells and is highly expressed in tumor cells ^[1]. SIRPα, a signal regulatory protein mainly expressed on macrophages, inhibits their phagocytosis of target cells by transmitting inhibitory signals when binding to CD47 on other cells. However, some tumor cells can evade phagocytosis and cause tumor immune escape by highly expressing CD47 and binding to SIRPα on macrophages, sending a “don’t eat me” signal. Targeting CD47 antibodies can initiate anti-tumor T cell immune responses and promote cancer-specific lymphocyte activation through macrophage-mediated phagocytosis of tumors. As a result, the CD47-SIRPα signaling pathway has great therapeutic potential and is a highly competitive target in tumor immunotherapy after PD-1/PD-L1 ^[1-2]. CD47 is a transmembrane protein with its extracellular domain serving as the receptor/ligand binding region and its intracellular domain responsible for signal transduction ^[3]. B6-hCD47 mice are obtained by replacing the fragment encoding the extracellular domain of CD47 protein in the mouse Cd47 gene with the corresponding human CD47 gene sequence, resulting in a model expressing the extracellular domain of human CD47 protein and the intracellular domain of mouse CD47 protein. This ensures normal binding with human antibodies and other protein drugs while completely retaining the intracellular part of mouse CD47 protein, maintaining normal intracellular signal transduction. B6-hCD47 mice can successfully express human CD47 protein and can be used for research on CD47-targeted inhibitors or antibody drug development and screening, pharmacology and safety evaluation, tumor immunotherapy evaluation, and mechanisms of tumor immune escape systems.