The MYC oncogene family comprises regulatory genes and proto-oncogenes that encode transcription factors, involved in various cellular processes such as the cell cycle, apoptosis, DNA repair, and metabolism. Members include c-Myc (MYC), l-Myc (MYCL), and n-Myc (MYCN). c-Myc (MYC) is a basic helix-loop-helix leucine zipper (bHLHZip) transcription factor, which forms heterodimers with Max protein to bind DNA and regulate the expression of approximately 15% of genes, thereby participating in key cellular processes such as cell proliferation, apoptosis, DNA repair, and metabolism. In many cancers, c-Myc is overexpressed, leading to uncontrolled cell proliferation and tumor growth, such as in Burkitt's lymphoma where c-Myc gene rearrangement is common. Dysregulation of the MYC oncogene plays a crucial role in tumorigenesis, predominantly through transcriptional dysregulation resulting in overexpression of c-Myc protein. Alb-Cre+/MYC+ mice are generated by crossing H11-CAG-LSL-hMYC-IRES-EGFP mice (Catalog Number: C001338), which conditionally express the human c-Myc oncogene, with Alb-Cre mice that express Cre recombinase specifically in hepatocytes under the control of the Alb promoter. The Cre-mediated recombination results in the deletion of the transcriptional stop sequence (Loxp-Stop-Loxp, LSL) in H11-CAG-LSL-hMYC-IRES-EGFP mice, leading to overexpression of the MYC oncogene in the liver and subsequent carcinogenesis. This model, therefore, spontaneously develops liver cancer with an early onset.

The immunoglobulin heavy chain constant region α1 (IGHA1) gene encodes the IgA1 protein, a subtype of immunoglobulin A (IgA), primarily found in mucosal areas such as the respiratory and gastrointestinal tracts, playing a key role in immune defense by neutralizing pathogens and preventing their invasion ^[1]. IgA nephropathy (IgAN) is one of the most common forms of glomerulonephritis, accounting for 30% to 50% of primary glomerulonephritis cases, and is a major cause of end-stage renal disease (ESRD). IgAN is characterized by the deposition of IgA1-containing immune complexes in the glomeruli (the kidney's filtering units), leading to extensive pathological damage ranging from mesangial matrix expansion to proliferative glomerulonephritis, ultimately manifesting as clinical symptoms such as hematuria and proteinuria, and impairing kidney function ^[2-3]. Approximately one-third of IgAN patients eventually progress to renal failure. The pathogenesis of IgAN is associated with galactose-deficient IgA1 (Gd-IgA1) in the serum, which acts as an autoantigen, triggering an immune response that leads to the formation and deposition of immune complexes in the kidneys ^[2-4]. Additionally, these IgA1 antibodies can bind to the soluble form of the myeloid IgA receptor FcαRI (CD89/FCAR), further exacerbating the disease ^[4]. The B6-hIgA1 mouse is a humanized model constructed by inserting the human IGHA1 gene sequence into the region between the mouse IgM enhancer (Eμ) and IgM constant region (Cμ), replacing the mouse IgM switch region (Sμ). B6-hIgA1 mice successfully express the human IGHA1 gene, and high levels of human IgA1 protein can be detected in their serum. Therefore, B6-hIgA1 mice can be used to study B cell development, immunoglobulin formation, and autoimmune mechanisms. They can also be crossed with CD89 humanized mouse models to create IgA nephropathy (IgAN) mouse model that better reflect human genetic mechanisms and pathological phenotypes ^[4], facilitating the development of IgA1-targeted drugs.

The SLC3A2 gene (Solute Carrier Family 3 Member 2), also known as CD98hc or 4F2hc, is ubiquitously expressed across many tissues and is often upregulated in various cancers, including lung, breast, and colorectal cancer. It encodes the cell-surface, transmembrane heavy chain of a heterodimeric amino acid transporter complex, which is covalently bound via disulfide bonds to a light chain from the SLC7A family (e.g., SLC7A5/LAT1 or SLC7A11/xCT). The primary function of the encoded protein is to act as a chaperone necessary for the light chain's proper plasma membrane localization and stability. The resulting functional complex transports specific essential amino acids; for instance, the SLC3A2/SLC7A5 dimer transports L-type neutral amino acids, while the SLC3A2/SLC7A7 dimer transports dibasic amino acids. This nutrient uptake is crucial for cell growth and metabolic reprogramming ^[1]. Beyond its transport role, SLC3A2 independently modulates integrin-dependent signaling pathways, affecting processes like cell spreading, adhesion, migration, and proliferation, which links it closely to cancer progression ^[2]. Cellular tissues with notable expression include trophoblasts (placenta), kidney proximal tubular cells, glandular cells (breast), Sertoli cells (testis), and various immune cells. SLC3A2 is primarily associated with cancer, where it acts as an oncoprotein and prognostic marker. It is also involved in specific cell death pathways like disulfidptosis ^[3]. Genetic associations have also been suggested between the SLC3A2 locus and conditions like schizophrenia, vitiligo, and Ulcerative Colitis, highlighting its broader role in cellular homeostasis ^[4]. B6-huCD98HC (huSLC3A2) mouse is a humanized model generated using gene editing technology, in which the mouse Slc3a2 endogenous extracellular domain is replaced with the human SLC3A2 extracellular domain. The murine cytoplasmic domain and transmembrane domain are preserved. This model can be used for research related to cancer, amino acid transport and metabolic intervention, immune regulation and autoimmunity, as well as the development of SLC3A2-targeted drugs.

The ITGB6 gene encodes the Integrin β subunit, a member of the integrin superfamily of adhesion receptors which are heterodimeric integral membrane proteins. This subunit pairs exclusively with the α subunit (encoded by ITGAV) to form the integrin αvβ6 heterodimer ^[1]. The primary function of the resulting αvβ6 protein is to mediate cell-to-extracellular matrix (ECM) signaling, particularly by binding to ECM ligands like fibronectin and, crucially, by activating latent transforming growth factor-β1 (TGF-β1), a cytokine that regulates tissue homeostasis, repair, and immune suppression. Gene expression is largely restricted to epithelial cells and is typically low or absent in healthy adult epithelia but is significantly upregulated in tissues undergoing development, wound healing, fibrosis, and in many cancers (e.g., pancreatic, colon, lung, oral squamous cell carcinoma) where its expression often correlates with poor prognosis and increased invasiveness ^[2]. Associated diseases include various forms of cancer, chronic organ fibrosis (such as pulmonary fibrosis), and rare genetic conditions like Amelogenesis Imperfecta and a syndrome characterized by alopecia and intellectual disability ^[3]. B6-hITGB6 mouse is a humanized model generated using gene editing technology, in which the sequence from aa.22 to partial intron 4 was replaced with Human ITGB6 CDS-Mouse Itgb6 CDS-3’UTR of Mouse Itgb6-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 forms of cancer, chronic organ fibrosis (such as pulmonary fibrosis), and rare genetic conditions, as well as for the development of ITGB6-targeted 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.

Complement component C3 plays a central role in activating the complement system and is the most abundant complement protein in human plasma, primarily synthesized in the liver. As part of the innate immune system, the complement system is activated during tissue damage and pathogen invasion, playing a crucial role in the inflammatory response, host homeostasis, and pathogen defense. The complement cascade is activated through the classical pathway, alternative pathway, and lectin pathway, all of which generate C3 convertase, which cleaves C3 into C3a and C3b. C3a is a potent anaphylatoxin with pro-inflammatory activity, while C3b is a regulator that induces C5 cleavage, thereby participating in the dissolution and clearance of immune complexes. Mutations in this gene are associated with atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration (AMD). Deficiencies in C3 and C3-derived peptides can lead to autoimmune diseases (such as rheumatoid arthritis, systemic lupus erythematosus, and vasculitis) and make individuals susceptible to recurrent respiratory infections and infections caused by encapsulated organisms. Conversely, excessive activation of C3 and related complement components is associated with kidney diseases (immune complex glomerulonephritis, hemolytic uremic syndrome, lupus nephritis, membranous nephropathy, and immune-mediated nephropathy) ^[1-2]. The Transferrin receptor (TFRC) gene encodes Transferrin Receptor 1 (TFR1), a protein that is expressed at low levels in most normal cells but shows increased expression in highly proliferative cells, such as basal epidermal cells, intestinal epithelium, and certain activated immune cells. Brain capillary endothelial cells, which constitute the blood-brain barrier (BBB), also express this receptor at high levels ^[3]. TFR1 plays a critical role in maintaining iron metabolism and homeostasis by facilitating receptor-mediated endocytosis of iron-bound transferrin (Tf) via Tf cycling, thereby promoting iron uptake ^[4]. Cellular iron deficiency can lead to apoptosis, while cellular transformation requires substantial iron to sustain proliferation, with iron overload contributing to tumor progression. The high expression of TFR1 in many tumors makes it a potential tumor marker, offering a target for therapies to inhibit tumor growth and metastasis ^[3]. Moreover, TFR1 is implicated in anemia and iron metabolism disorders. Studies have shown that elevated TFR1 expression in cardiomyocytes is associated with exacerbated inflammation in myocarditis patients ^[5]. Various clinical drugs targeting TFR1 are currently under development, including antisense oligonucleotides (ASOs), antibody-drug conjugates (ADCs), and antibody-oligonucleotide conjugates, applicable to diseases such as cancer, anemia, and neurodegenerative disorders. Research indicates that enhancing antibody transport across the blood-brain barrier via TFR1, by forming specific bispecific antibodies with anti-β-amyloid antibodies, can improve therapeutic outcomes in Alzheimer's patients ^[6-7]. As research progresses, TFR1 is expected to become an effective clinical target for multiple diseases and a synergistic target for drug delivery across the blood-brain barrier (BBB). The B6-hC3/hTFRC(CDS) mouse model is a humanized model obtained by breeding huC3 mice (Catalog No.: C001955) with B6-hTFRC(CDS) mice (Catalog No.: C001584). This model can be used for research on complement-mediated diseases, iron metabolism disorders, neurodegenerative diseases, and tumor development, aiding in studying C3/TFRC-targeted drugs.

The IL6RA (IL6R, also known as CD126) gene encodes a subunit of the interleukin-6 (IL-6) receptor complex. The IL-6 receptor is a protein complex composed of the IL6RA protein and the interleukin-6 signal transducer (IL6ST/GP130/IL6-beta). This receptor subunit is shared by many other cytokines. The expression of IL-6R is primarily restricted to hepatocytes, leukocytes, and megakaryocytes. Upon binding to its receptor IL-6Rα, IL-6 interacts with two GP130 molecules to form a hexameric complex in a 2:2:2 configuration. Once the IL-6 receptor complex is activated, multiple downstream events allow IL-6 to mediate its diverse effects. These include the pathways of the GTPase Ras and its effector Raf, the mitogen-activated protein kinase cascade that controls cellular proliferation and differentiation, and the pathways involving tyrosine kinases of the Jak family and transcription factors of the STAT family ^[1]. IL-6 receptor defects can lead to immunodeficiency and atopy. Patients with loss-of-function variants in IL-6R present with an autosomal recessive disorder characterized by recurrent Haemophilus chest infections, staphylococcal skin abscesses, atopic dermatitis, elevated IgE levels, eosinophilia, and absent acute phase responses ^[2]. Research has shown that the IL-6 pathway is crucial for maintaining homeostasis and is involved in the dysregulation seen in many diseases. Antibody drugs targeting the IL-6/IL-6 receptor signaling pathway have become innovative therapies for autoimmune diseases and cancers ^[3]. The B6-hIL6RA mouse is an Il6ra gene humanized model, in which the coding sequence (CDS) of the human IL6R gene is inserted into the endogenous Il6ra gene sequence of mice. This model can be used in researching autoimmune diseases, inflammation-related diseases, cancer, and infectious diseases. It is also useful for the development, screening, and evaluation of IL6RA-targeted drugs.

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 BALB/c-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 (aa.79~271) will be replaced with the human TNFSF15 extracellular domain (aa.57~252). The homozygous BALB/c-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.

The TNFRSF9 gene, also known as 4-1BB/CD137, encodes a protein that belongs to the TNF receptor superfamily. This receptor aids in the clonal expansion, survival, and development of T cells. It can also induce the proliferation of peripheral monocytes, enhance TCR/CD3-triggered activation-induced T cell apoptosis, and regulate CD28 co-stimulation to promote Th1 cell responses. TRAF adaptor proteins can bind to it and transmit signals that activate NF-kappaB. Many immune cell types express TNFRSF9, including activated NK cells, NKT cells, B cells, eosinophils, basophils, mast cells, neutrophils, mature Tregs, activated monocytes, and dendritic cells. Additionally, TNFRSF9 may be expressed in non-immune cell types such as endothelial cells, neurons, astrocytes, and microglia. TNFRSF9 plays roles in innate and adaptive immunity, including cancer immunology and autoimmune diseases ^[1]. Due to its broad expression profile and immune response functions, 4-1BB is a potential target for cancer and immunotherapy. In recent years, research on second-generation 4-1BB agonists has been expanding, with various strategies being implemented to overcome the liver toxicity and efficacy limitations of the first generation ^[2-3]. The B6-h4-1BB(TNFRSF9) mouse is a humanized model. The sequence encoding the endogenous extracellular domain of the mouse Tnfrsf9 is replaced in situ with the sequence encoding the human TNFRSF9 extracellular domain. This model can be used for studies on cancer immunology and autoimmune diseases, as well as for the development, screening, and evaluation of 4-1BB agonists in preclinical research.

The KLB gene encodes β-Klotho, a transmembrane protein that functions as an obligate co-receptor for fibroblast growth factor (FGF) receptors, specifically for the endocrine FGF ligands FGF19 and FGF21 ^[1]. Expressed across metabolic tissues, including adipose, liver, and pancreas, KLB is a critical regulator of FGF19 and FGF21 signaling, impacting glucose homeostasis, energy balance, and bile acid metabolism ^[1-3]. β-Klotho facilitates FGF19 and FGF21 signaling through direct interaction with FGF receptors ^[1]. KLB gene expression is observed across various tissues, encompassing metabolic, haematopoietic, foetal, and adult tissues ^[1]. Perturbations in KLB function and genetic variants have been implicated in a range of disorders, including hypogonadotropic hypogonadism, male infertility, obesity, non-alcoholic fatty liver disease, irritable bowel syndrome, and potentially certain malignancies ^[1-4]. Thus, KLB emerges as a pivotal gene in FGF signaling, exerting pleiotropic effects on metabolic physiology and disease ^[1-4]. The B6-hKLB mouse is a humanized model generated using gene editing technology by integrating the Chimeric cDNA and the 3'UTR of the mouse Klb gene into the mouse Klb gene locus. The mouse Klb endogenous extracellular domain was replaced with the human KLB domain, and the murine transmembrane-cytoplasmic region was remained. Homozygous B6-hKLB mice are viable and fertile. This model can be used for research on the pathological mechanisms and treatment methods of metabolic diseases such as obesity, diabetes, metabolic-associated steatohepatitis (MASH), inflammatory diseases, and potentially selected malignancies and the development of KLB-targeted drugs.