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 Cryopyrin protein, encoded by the NOD-like receptor family pyrin domain-containing 3 (NLRP3) gene, is a core component of the inflammasome in the innate immune system. As a member of the NOD-like receptor (NLR) family, NLRP3 is predominantly expressed in leukocytes and chondrocytes. It participates in the host defense against damage and infection by recognizing pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) to activate immune responses ^[1]. In its inactive monomeric state, NLRP3 senses intracellular damage signals, such as abnormal protein aggregates and lipid accumulation. Upon activation, NLRP3 oligomerizes, adopting an active conformation and assembling into inflammasome complexes, subsequently activating Caspase-1 to drive the maturation and secretion of pro-inflammatory cytokines, including IL-1β and IL-18 ^[1-2]. Activated NLRP3 not only induces the release of inflammatory cytokines but also triggers lytic cell pyroptosis. The intracellular components released during pyroptosis can further amplify inflammatory signals, forming a positive feedback loop of autoinflammation. Moreover, IL-1β can exacerbate the inflammatory cascade by stimulating the production of inflammatory markers such as IL-6 and high-sensitivity C-reactive protein (hsCRP) ^[3-4]. Given NLRP3's upstream position relative to IL-1β/IL-18 and other inflammatory factors, targeting its activity can effectively block the self-reinforcing mechanism of chronic inflammation, providing a significant therapeutic strategy for inflammation-related diseases ^[5]. The potential therapeutic areas include Alzheimer’s disease, Parkinson’s disease (via neuroinflammation modulation), inflammatory bowel disease, metabolic dysfunction-associated steatohepatitis (MASH), gout, and obesity-related metabolic inflammation ^[6-7]. The B6-hNLRP3 mouse model was generated by replacing the mouse Nlrp3 genomic region (from the ATG start codon to downstream of the 3'UTR) with the human NLRP3 sequence (from upstream of the ATG start codon to downstream of the 3'UTR), enabling stable expression of human NLRP3 protein. The B6-hNLRP3 mouse is suitable for studying inflammatory mechanisms, autoimmune diseases, neurodegenerative diseases, and metabolic diseases. It also serves as an ideal tool for human NLRP3-targeted drug development and preclinical efficacy evaluation.

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 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 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.

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.