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.

The CD7 gene encodes a transmembrane glycoprotein belonging to the immunoglobulin superfamily (IgSF). As an important co-receptor on the T cell surface, CD7 plays a critical regulatory role in T cell activation, proliferation, and signal transduction. CD7 is primarily expressed on T cells and natural killer (NK) cells, with expression observed from the early stages of thymocyte development through to mature T cells. It is also expressed in some hematopoietic progenitor cells, but its expression level is relatively low in most normal non-T/NK cell tissues ^[1]. Aberrant expression or dysregulated signaling of CD7 is closely associated with various diseases. As a key therapeutic target in immunotherapy, CD7 is highly expressed in T cell acute lymphoblastic leukemia (T-ALL) and T cell lymphomas, making it a critical molecule for targeting T cell malignancies ^[1]. In addition, CD7 is associated with systemic sclerosis (SSc) and graft-versus-host disease (GvHD) ^[2-3]. Currently, multiple therapeutic strategies targeting CD7 are under development, including anti-CD7 CAR-T cell therapy, CD7 CAR-iNK cells, and bispecific CAR-T therapies targeting CD7, which have demonstrated promising preclinical and early clinical potential in relapsed/refractory T-ALL and T cell lymphomas ^[4-5]. The huCD7 mouse is a humanized model generated using gene editing technology, in which the endogenous signal peptide and extracellular domain sequence of the mouse Cd7 gene were replaced with the corresponding sequence of the human CD7 gene. This model is suitable for the in vivo efficacy and safety evaluation of antibody drugs and CAR-T cell therapies targeting human CD7, as well as for studies on T cell development and function. It also serves as an ideal platform for investigating the functional mechanisms of CD7⁺ T cells in T cell acute lymphoblastic leukemia (T-ALL), T cell lymphomas, and autoimmune diseases such as systemic sclerosis (SSc).

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.

The SCN10A gene, which encodes the sodium channel Na(v)1.8, is a susceptibility factor for cardiac conduction block and severe ventricular arrhythmias. Genetic variations in ion channel genes are associated with hereditary arrhythmias, such as Long QT Syndrome, Short QT Syndrome, Brugada Syndrome (BrS), and conduction abnormalities. These variations are also linked to sudden unexplained death (SUD) in young adults and children. Several studies have identified common variants of SCN10A as potential regulators of human PR and QRS durations, with SCN10A being a major susceptibility gene for BrS ^[1-2]. The Nav1.8 protein is expressed in small-diameter sensory neurons of the trigeminal ganglion and dorsal root ganglion (DRG), as well as in some medium- and large-diameter neurons and in layers I and II of the spinal dorsal horn ^[3]. The SCN10A/Nav1.8 voltage-gated sodium channel is crucial in pain management. Studies have shown that Nav1.8 channel inhibitors have the potential to become a new class of effective analgesics suitable for multimodal pain treatment in postoperative patients. Additionally, the low expression of SCN10A in the brain suggests a lower likelihood of adverse effects, including dependency and abuse, within the central nervous system ^[4]. In early 2025, the FDA approved Suzetrigine, a Nav1.8 inhibitor developed by Vertex Pharmaceuticals, marking a breakthrough in the pain management field previously dominated by opioid drugs. As the first non-opioid acute pain medication in two decades, the success of Suzetrigine is a significant milestone. hSCN10A(Nav1.8)(SD) rats are a Scn10a humanized model created by inserting the human SCN10A gene's coding sequence (CDS) and 3'UTR into the rat Scn10a gene. This model can be used for mechanistic studies of acute pain and diabetic peripheral neuropathic pain and the development, screening, and evaluation of analgesic drugs in preclinical research. During the production of this rat strain, scratching behavior was observed after weaning and cage separation, resulting in skin lesions. Trimming the nails at the time of cage separation effectively prevents such skin damage. For long-term prevention, nail trimming should be repeated every 2 weeks.

The CRBN gene, located on human 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 diseases, such as multiple myeloma, leading to the development of diverse therapeutic modalities including molecular glues and proteolysis targeting chimeras (PROTACs) ^[3-5]. 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 (ARNSID), 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 human 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 (TPD/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 diseases, such as multiple myeloma, leading to the development of diverse therapeutic modalities including molecular glues and proteolysis targeting chimeras (PROTACs) ^[3-5]. hCRBN(BALB/c) 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 the 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 (TPD) therapies.

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]. huIL4RA 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 huIL4RA 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.