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.

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.

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 FGFR1 gene provides instructions for the synthesis of the fibroblast growth factor receptor 1, a member of the receptor tyrosine kinase (RTK) family. This protein is characterized by an extracellular region with three immunoglobulin-like domains for ligand binding, a single transmembrane segment, and an intracellular tyrosine kinase domain that triggers downstream signaling cascades like the MAPK/ERK and PI3K/AKT pathways. FGFR1 is widely expressed across diverse tissues, with particularly high levels in the developing mesoderm, skeletal system, and the central nervous system, where it is essential for the migration of gonadotropin-releasing hormone (GnRH) neurons and olfactory bulb development ^[1]. Functionally, it acts as a master regulator of cell proliferation, differentiation, and survival, playing a pivotal role in embryonic limb induction and adult tissue homeostasis ^[2]. Mutations or chromosomal aberrations in FGFR1 are linked to a diverse array of diseases: gain-of-function mutations cause craniosynostosis syndromes like Pfeiffer and Jackson-Weiss syndromes, while loss-of-function variants lead to Kallmann syndrome (characterized by delayed puberty and an absent sense of smell) ^[3]. Additionally, FGFR1 gene amplifications and rearrangements are significant oncogenic drivers in various cancers, including squamous cell lung cancer, certain breast cancers, and 8p11 myeloproliferative syndrome ^[4]. The B6-huFGFR1 mouse is a humanized model constructed through gene-editing technology, in which the mouse Fgfr1 endogenous extracellular domain genomic DNA is replaced with the human FGFR1 extracellular domain genomic DNA. This model can be used for research on craniosynostosis syndromes, Kallmann syndrome, and various cancers, as well as for screening, development, and preclinical evaluation of FGFR1-targeted therapeutics.

The IL12B gene encodes the p40 subunit, a component of both interleukin-12 (IL-12) and IL-23, which are formed through heterodimerization with IL-12p35 and IL-23p19, respectively ^[1]. Primarily secreted by activated monocytes, macrophages, dendritic cells, and B lymphocytes, these cytokines modulate Th1 and Th17 cell differentiation via the JAK-STAT signaling pathway, playing critical roles in immunity against intracellular pathogens and in inflammatory responses. IL-12 also enhances cellular immunity through the induction of interferon-gamma ^[1-2]. IL12B gene expression is regulated by NF-κB and IRF transcription factors, and aberrant activation is implicated in autoimmune pathogenesis. Notably, single nucleotide polymorphisms (SNPs) within IL12B and an overactive IL-12/IL-23 pathway are strongly associated with susceptibility to autoimmune diseases ^[1-3]. Monoclonal antibodies targeting IL-12B, such as ustekinumab, are clinically utilized for the treatment of moderate to severe psoriasis and Crohn's disease ^[4-5]. Within the tumor microenvironment, IL-12B exhibits a complex functional profile, potentially enhancing cytotoxic T and NK cell activity, promoting IFN-γ production, and driving anti-tumor immunity. However, it can also contribute to tumor progression by fostering angiogenesis, depending on the tumor type and microenvironmental context ^[6]. This duality underscores IL-12B as a key target for precise immunotherapy, particularly in combination therapies that simultaneously block IL-12 and IL-23 signaling, offering therapeutic potential across a spectrum of immune-related diseases and cancers ^[1-6]. B6-huIL12B mice are humanized models generated by gene editing technology, in which the entire base sequence of the mouse Il12b gene was replaced in situ with the corresponding sequence from the human IL12B gene. Homozygous B6-huIL12B mice are viable and fertile. This model can be used to study the pathological mechanisms and therapeutic methods of immune-related diseases and cancer, as well as the screening and development of IL12B-targeted drugs, and preclinical efficacy and safety evaluations.

MMP7 encodes matrix metalloproteinase-7 (MMP-7), also known as matrilysin, a member of the matrix metalloproteinase family that plays a crucial role in the degradation and remodeling of extracellular matrix (ECM) components ^[1]. MMP7 is primarily expressed in epithelial tissues of the gastrointestinal tract, lungs, and reproductive system. Cytokines, growth factors, hypoxia, and inflammatory signals regulate its expression. MMP7 is secreted as a zymogen and activated by other proteases or autolytic cleavage. Activated MMP7 can degrade ECM components such as collagen, proteoglycans, elastin, and fibronectin, and can also activate antimicrobial peptides (e.g., defensins) and process cytokines ^[2]. Functionally, MMP7 involves various physiological and pathological processes, including ECM remodeling, immune regulation, wound healing, and tumor progression. It is notably significant in tumor invasion and metastasis, where it promotes cancer cell migration by degrading matrix barriers and accelerates tumor growth by regulating angiogenesis and immune evasion ^[2-3]. MMP7 is associated with several diseases, including cancers (e.g., colorectal, gastric, pancreatic, and lung cancers, with high expression often correlated with poor prognosis), inflammatory diseases (e.g., inflammatory bowel disease, chronic obstructive pulmonary disease, and asthma), fibrotic diseases (e.g., idiopathic pulmonary fibrosis), and cardiovascular diseases (e.g., atherosclerosis and aneurysms) ^[3-5]. Hence, MMP7 is an important therapeutic target for various diseases. However, clinical trials targeting MMP7 face challenges in efficacy and safety. Broad-spectrum MMP inhibitors (e.g., Marimastat and Batimastat) have limited efficacy due to low specificity and adverse effects like musculoskeletal pain. Recent research focuses on selective MMP7-targeted inhibitory therapies, including small molecule inhibitors, monoclonal antibodies, peptide inhibitors, small interfering RNA (siRNA), and antisense oligonucleotides (ASO) ^[5-8]. MMP7 plays dual roles in maintaining physiological homeostasis and mediating pathological processes (particularly in cancer and fibrosis), making it a promising yet challenging therapeutic target. The B6-huMMP7 mouse is a humanized model constructed by gene-editing technology. The sequences from upstream of exon 1 to downstream of exon 6 of the mouse Mmp7 gene were replaced with the sequences from upstream of exon 1 to downstream of exon 6 of the human MMP7. This model can be used for the research of various cancers, inflammatory diseases, fibrotic diseases, and cardiovascular diseases, as well as for the development of MMP7-targeted drugs.