The adenomatous polyposis coli (APC) gene is a tumor suppressor gene, the protein it encodes plays a key regulatory role in the Wnt/β-catenin signaling pathway ^[1]. The APC protein can antagonize the Wnt signaling pathway, assisting in regulating cell migration, adhesion, transcriptional activation, and apoptosis. More than 10% of human tumors have mutations in the APC gene, and most colorectal cancers have mutations in the APC gene ^[2]. Defects in the APC gene lead to the occurrence of familial adenomatous polyposis (FAP), characterized by hundreds to thousands of adenomatous polyps in the rectum. This is an autosomal dominant precancerous disease, which usually develops into malignant tumors ^[1-2]. Disease-related mutations in the APC gene are highly prevalent in a small region known as the mutation cluster region (MCR), which usually leads to the production of truncated proteins ^[3-4]. In mice, either Apc gene deletion or multiple intestinal neoplasia (Min) mutations that result in the production of truncated APC proteins cause phenotypes similar to human familial adenomatous polyposis (FAP) and/or colorectal tumors ^[5-9]. The Apc-KO mouse is a research model constructed by using gene editing technology to knock out the sequence in the mouse Apc gene that contains the mutation cluster region (MCR), and this strain is homozygous lethal. Heterozygous Apc-KO mice can spontaneously develop intestinal adenomas and exhibit significant colorectal cancer disease phenotypes in various aspects such as survival, growth, food intake, and intestinal lesions. Therefore, Apc-KO mice can be used for familial adenomatous polyposis (FAP) and colorectal cancer and other tumors or tumor-related diseases, as well as the study of the regulatory mechanism of the Wnt/β-catenin signaling pathway.

P-glycoprotein (P-gp), also known as multidrug resistance protein 1 (MDR1), is an ATP-binding cassette transporter that acts as a biological barrier by expelling toxins and foreign substances from cells. P-gp is capable of transporting many structurally and functionally different compounds out of cells ^[1]. However, the mechanism of MDR1 also prevents the uptake of many cancer treatment drugs by cells, leading to multidrug resistance (MDR) ^[2]. In normal organisms, MDR1’s distribution in the blood-brain barrier and blood-placenta barrier prevents exogenous drugs and toxins from entering the central nervous system and placenta of the organism, thereby protecting the organism and enabling it to perform normal physiological functions. In pathological conditions, however, the MDR1 in the blood-brain barrier prevents drugs from entering the central nervous system, and in tumor cells, leads to the development of MDR. The evolution of MDR remains one of the major obstacles to controlling or curing cancer ^[3-4]. In humans, the MDR1 protein is encoded by the ABCB1 gene. In mice, two closely located genes, Abcb1a and Abcb1b, encode the MDR1a and MDR1b subtypes of this protein. Mouse MDR1a and MDR1b have 80% homology with human MDR1. MDR1a and MDR1b have the same function as human MDR1 protein in resisting anticancer drugs. Although mouse MDR1a and MDR1b proteins are distributed in different tissues of the body, their overall distribution is consistent with that of human MDR1 protein ^[5-6]. In summary, the distribution and function of mouse MDR1a and MDR1b are consistent with those of human MDR1. This strain is an MDR1 knockout model, in which the human ABCB1 gene’s homologous genes, Abcb1a and Abcb1b, were knocked out in mice using gene editing technology. This model lacks the expression of MDR1 protein and can be used for research in areas such as blood-brain barrier permeability-related diseases and multidrug resistance of anti-tumor drugs.

The ITGAV gene encodes the Integrin subunit α V (also known as αv or CD51), a transmembrane glycoprotein that is a member of the integrin superfamily. The encoded preproprotein is proteolytically processed into light and heavy chains that form the αv subunit, which then heterodimerizes with various β subunits (specifically β1, β3, β5, β6, or β8) to create functional receptors, with the αv β3 heterodimer being famously known as the vitronectin receptor ^[1]. αv integrins function as essential cell surface adhesion and signaling receptors that mediate interactions with the extracellular matrix (ECM) ligands, often recognizing the Arg-Gly-Asp (RGD) sequence, playing a crucial role in cell adhesion, migration, proliferation, angiogenesis, and the activation of latent growth factors like TGF-β1 ^[2]. While generally expressed at low levels in most healthy tissues, ITGAV is notably found on various cell types, including endothelial cells, macrophages, osteoclasts, synovial fibroblasts, and mesenchymal stromal cells, and its expression is often highly upregulated in various pathological conditions, including several cancers (e.g., hepatocellular, prostate, colorectal, esophageal, and head and neck squamous cell carcinoma), where its overexpression is frequently associated with poor prognosis and metastasis; additionally, ITGAV is implicated in autoimmune diseases such as rheumatoid arthritis (RA) and is exploited by various viral infections (e.g., West Nile virus, Adenovirus) ^[3]. B6-hITGAV mouse is a humanized model generated using gene editing technology, in which the sequence from partial exon 1 to partial intron 1 of mouse Itgav is replaced with ITGAV chimeric CDS-WPRE-BGH pA cassette. The murine signal peptide was preserved. This model can be used for studying the pathological mechanisms and therapeutic approaches of various cancers, autoimmune diseases such as rheumatoid arthritis (RA), and various viral infections, as well as for the development of ITGAV-targeted drugs.

Cluster of differentiation 3 (CD3) is a multimeric protein complex that is essential for T cell activation and antigen recognition. It consists of five different polypeptide chains (γ, δ, ε, ζ, and η) that are noncovalently associated with the T cell receptor (TCR). The TCR is responsible for recognizing antigens presented by antigen-presenting cells (APCs), while CD3 transduces the activation signal into the T cell and activates helper T-cells and cytotoxic T-cells ^[1-2]. The CD3-TCR complex is expressed on the surface of all mature T cells, and its assembly is required for T cell development and function. CD3 plays a crucial role in stabilizing the TCR and facilitating its interaction with antigens. It also recruits signaling molecules to the TCR, which initiates a cascade of events that leads to T cell activation. CD3 is a highly specific T cell marker, and its expression is increased upon T cell activation. This makes it a valuable tool for identifying and characterizing T cells in tissues and blood samples. CD3 staining is also used to diagnose T-cell lymphomas and leukemias. Due to its essential role in T cell activation, CD3 is a promising target for immunosuppressive therapy. Several anti-CD3 monoclonal antibodies have been developed and are being tested in clinical trials for the treatment of autoimmune diseases, such as type 1 diabetes and rheumatoid arthritis ^[3]. The BALB/c-hCD3 mice are a CD3 humanized model obtained by replacing the mouse CD3 coding gene with the human CD3 gene using embryonic stem (ES) cell targeting technology. This model can be used to study T cell activation and antigen recognition mechanisms and for the development of CD3-targeted drugs in immunosuppressive therapies for autoimmune diseases.

Cluster of differentiation 3 (CD3) is a multimeric protein complex that is essential for T cell activation and antigen recognition. It consists of five different polypeptide chains (γ, δ, ε, ζ, and η) that are noncovalently associated with the T cell receptor (TCR). The TCR is responsible for recognizing antigens presented by antigen-presenting cells (APCs), while CD3 transduces the activation signal into the T cell and activates helper T-cells and cytotoxic T-cells ^[1-2]. The CD3-TCR complex is expressed on the surface of all mature T cells, and its assembly is required for T cell development and function. CD3 plays a crucial role in stabilizing the TCR and facilitating its interaction with antigens. It also recruits signaling molecules to the TCR, which initiates a cascade of events that leads to T cell activation. CD3 is a highly specific T cell marker, and its expression is increased upon T cell activation. This makes it a valuable tool for identifying and characterizing T cells in tissues and blood samples. CD3 staining is also used to diagnose T-cell lymphomas and leukemias. Due to its essential role in T cell activation, CD3 is a promising target for immunosuppressive therapy. Several anti-CD3 monoclonal antibodies have been developed and are being tested in clinical trials for the treatment of autoimmune diseases, such as type 1 diabetes and rheumatoid arthritis ^[3]. The BALB/c-hCD3 (line2) mice are a CD3 humanized model obtained by replacing the mouse CD3 coding gene with the human CD3 gene using embryonic stem (ES) cell targeting technology. This model can be used to study T cell activation and antigen recognition mechanisms and for the development of CD3-targeted drugs in immunosuppressive therapies for autoimmune diseases.

The interleukin-2 receptor alpha subunit, encoded by the IL2RA gene and also known as CD25, is a critical determinant of IL-2 signaling, a pathway fundamental to T cell biology. While CD25 alone exhibits low affinity for IL-2, its assembly with the IL-2 receptor beta and gamma chains forms the high-affinity receptor complex essential for robust cellular responses to this pleiotropic cytokine ^[1]. Expressed prominently on activated T lymphocytes, including effector and regulatory T cells, CD25 is pivotal for diverse processes such as T cell proliferation, differentiation, and the maintenance of immune tolerance, largely mediated through its indispensable role in regulatory T cell development and function ^[2]. Consequently, perturbations in IL2RA expression or genetic variants within the locus are strongly associated with susceptibility to a range of severe autoimmune disorders, including multiple sclerosis, type 1 diabetes, and rheumatoid arthritis, highlighting its central involvement in immune homeostasis breakdown ^[3]. Furthermore, aberrant CD25 expression has been observed in certain malignancies, suggesting roles beyond adaptive immunity ^[4]. The demonstrable impact of IL2RA on immune regulation and disease pathogenesis underscores its significance as a key molecule in immunology and a compelling target for therapeutic intervention. The B6-hIL2RA mouse is a humanized model constructed by replacing the sequence of the mouse Il2ra endogenous extracellular domain in situ with the corresponding extracellular domain from the human IL2RA. The murine signal peptide and transmembrane-cytoplasmic region were preserved. The B6-hIL2RA mice can be used for the study of the pathogenesis of autoimmune diseases such as multiple sclerosis, type 1 diabetes, and rheumatoid arthritis, and certain malignancies, as well as for IL2RA-targeted drug development.

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.

The TGFB2 gene encodes transforming growth factor-beta 2 (TGF-β2), a secreted multifunctional cytokine that regulates cell proliferation, differentiation, apoptosis, and extracellular matrix production ^[1]. It is expressed in various tissues, including epithelial cells, mesenchymal cells, immune cells, and neural tissues, playing critical roles in embryonic development, immune regulation, and tissue homeostasis. The encoded protein is synthesized as an inactive precursor that undergoes proteolytic cleavage to release the active TGF-β2 ligand, which signals through SMAD-dependent and SMAD-independent pathways ^[1]. Dysregulation of TGFB2 is linked to cardiovascular diseases (e.g., Marfan syndrome, aortic aneurysms), fibrosis, cancer (both tumor-suppressive and pro-metastatic roles), and developmental disorders (e.g., Loeys-Dietz syndrome) ^[2-3]. Additionally, TGFB2 mutations or aberrant expression can contribute to ocular defects, craniofacial abnormalities, and immune dysregulation ^[4]. Its pleiotropic effects make it essential in both normal physiology and disease pathogenesis. The B6-hTGFB2 mouse is a humanized model, constructed by replacing the partial coding sequences of mouse Tgfb2 exon 1 with the Kozak-Human TGFB2 CDS-3’UTR of the Human TGFB2-WPRE-BGH pA cassette. B6-hTGFB2 mice can be used for research into the pathogenesis of cardiovascular diseases, fibrosis, cancers, and developmental disorders. They are also useful for the screening, development, and safety evaluation of TGFB2-targeted drugs.