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+/hMYC-IRES-EGFP+ 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 HRas oncogene (HRAS), also known as the Harvey Rat Sarcoma Viral Oncogene Homolog (HRAS), is a member of the Ras oncogene family, which also includes KRAS and NRAS. All members of this family are associated with the development of mammalian sarcoma retroviruses ^[1]. HRAS encodes the H-Ras protein, a small GTPase responsible for transmitting signals from cell surface receptors to the nucleus, regulating cell proliferation, survival, and differentiation. HRAS is primarily expressed in various tissues, including the brain, heart, and skeletal muscle, and is involved in controlling the cellular response to growth factors. As a member of the small GTPase family, HRAS acts as a molecular switch, cycling between active and inactive states to influence key cellular processes. Mutations in the HRAS gene can lead to abnormal signal transduction, commonly found in tumors of stratified epithelial tissues, such as bladder cancer, thyroid cancer, and head and neck squamous cell carcinoma. Additionally, HRAS is associated with Costello syndrome, a genetic disorder characterized by developmental delays and an increased risk of tumors ^[2-3]. Early studies have shown that genotoxic carcinogens shorten the latency period and increase the incidence of malignant tumors in rasH2 mice, which carry the human HRAS (c-Ha-ras) oncogene, compared to non-transgenic mice. Therefore, rasH2 mice are ideal animal models for rapid carcinogenicity testing ^[4-5]. Further research has shown that F1 hybrid mice (CB6F1 background rasH2 mice) obtained by mating male C57BL/6J mice carrying the human prototype c-Ha-ras gene with female BALB/c mice are significantly more sensitive to both mutagenic and non-mutagenic carcinogens than control mice ^[5]. These mice are highly sensitive to the carcinogenicity of both genotoxic and non-genotoxic compounds while showing no response to non-carcinogens ^[6]. Between 12 to 18 months of age, rasH2 mice primarily develop spontaneous alveolar adenomas/bronchial adenomas/adenocarcinomas, splenic hemangiomas/hemangiosarcomas, and a smaller number of skin and gastric papillomas and lymphomas ^[4]. In the 1990s, this mouse model was officially approved by the FDA for carcinogenicity evaluations in drug safety assessments, reducing the standard two-year carcinogenicity test in common rodents to six months. BALB/c;B6J-Rosa26-hHRAS mice are obtained by crossing Rosa26-hHRAS mice on a C57BL/6JCya background (Catalog No.: I001213) with BALB/cAnCya mice. This hybrid strain exhibits higher sensitivity to both genotoxic and non-genotoxic human carcinogens. BALB/c;B6J-Rosa26-hHRAS mice can be used for rapid in vivo testing of the carcinogenicity of genotoxic and non-genotoxic compounds, studying the impact of HRAS oncogene point mutations on tumorigenesis and development, and developing tumor prevention or suppression therapies.

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 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 ^[6]. 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 ^[6-7]. 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) ^[8-9]. 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 ^[10]. 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 ^[11-12]. B6-hTL1A/hNLRP3 mice are TL1A and NLRP3 double humanized mouse models obtained by mating TL1A humanized mouse models (Catalog No. C001603) with NLRP3 humanized mouse models (Catalog No. C001616). B6-hTL1A/hNLRP3 mice express human TL1A and NLRP3 genomic sequences under the control of mouse promoters. This model is capable of reproducing human TL1A and NLRP3 and is a valuable tool for studying autoimmune diseases and inflammation-related diseases. In addition, this model also provides a powerful preclinical research platform for evaluating the efficacy and mechanism of therapeutic drugs targeting TL1A and NLRP3.

The B6-huTFRC/huACVR2B mouse is a dual-gene humanized model obtained by mating B6-huTFRC mice (catalog No.: C001860) with B6-huACVR2B mice (catalog No.: C001904). This model can be used in the research of muscle atrophy and growth regulation, tumorigenesis and development, reproduction and gonadal function, iron metabolism diseases, and neurodegenerative diseases, and it helps with the development of TFRC/ACVR2B-targeted drugs and preclinical pharmacological and efficacy evaluations.

CD89, also known as Fcα receptor (FCAR), is a receptor on the surface of various immune cells and belongs to the Fc receptor family. Fc receptors bind antibodies, linking the immune system’s recognition of pathogens with cellular immune responses. CD89 is primarily expressed on monocytes/macrophages, neutrophils, eosinophils, dendritic cells, and Kupffer cells in the liver, unlike other Fc receptors expressed on lymphocytes ^[1]. The function of CD89 primarily involves binding with IgA antibodies (especially IgA1 and IgA2), initiating various immune responses. CD89 can trigger phagocytosis (engulfing and destroying pathogens), antibody-dependent cellular cytotoxicity (ADCC) (killing infected or cancerous cells), and release inflammatory mediators (promoting inflammatory responses and recruiting immune cells) ^[2]. IgA nephropathy (IgAN) is a disease closely associated with CD89 and is the most common form of glomerulonephritis, characterized by the deposition of IgA (particularly IgA1) in the glomeruli. As the myeloid cell-specific Fc receptor for IgA, CD89 specifically binds IgA1, a highly glycosylated IgA subtype predominantly found in serum and responsible for neutralizing pathogens at mucosal surfaces ^[3-4]. In IgA nephropathy, one pathological mechanism is the formation of immune complexes between aberrantly glycosylated IgA1 and CD89. These complexes deposit in the glomerular mesangium, activate mesangial cells, and trigger inflammation, fibrosis, and kidney structural damage. Without treatment, the condition can progress to chronic kidney disease (CKD) and even end-stage renal disease (ESRD) ^[5-7]. Since mice lack a homologous gene to human CD89, introducing the human CD89 gene into mice aids in studying immune mechanisms and IgA nephropathy (IgAN). The Cd11b-hCD89(FCAR) mice are a humanized model constructed by integrating the coding sequence (CDS) of the human CD89 gene downstream of the TAA stop codon of the mouse Cd11b (Itgam) gene. The human CD89 gene is specifically expressed in myeloid cells under the regulation of the mouse Cd11b gene promoter. Cd11b-hCD89(FCAR) mice can be used in studies on immune responses, autoimmune mechanisms, as well as tumor and infectious diseases. They can also be crossed with the IgA1 humanized mouse model (Product No.: C001565) to construct an IgA nephropathy (IgAN) mouse model that better recapitulates human genetic mechanisms and pathological phenotypes ^[8], for researching IgAN mechanisms and developing therapies.

The FGFR3 gene encodes Fibroblast Growth Factor Receptor 3, a transmembrane receptor tyrosine kinase that plays a crucial role in regulating cell growth, differentiation, and apoptosis. It is widely expressed in various tissues, including the brain, kidney, testis, lung, small intestine, and liver, but is particularly important in cells forming bones, especially within the growth plate of cartilage ^[1]. The Fgfr3*Y367C mutation, which corresponds to the human Y373C mutation (a gain-of-function mutation), leads to constitutive activation of the FGFR3 protein. This overactivity disrupts normal chondrocyte proliferation and differentiation, impairing endochondral ossification and linear bone growth ^[2]. As a result, this mutation is significantly associated with severe skeletal dysplasias, including Thanatophoric Dysplasia type I (TDI) and Achondroplasia (ACH), the most common form of short-limbed dwarfism, characterized by disproportionate short stature, macrocephaly, and other skeletal deformities ^[3]. Y373C is one of the common activating mutations of FGFR3, accounting for approximately 50% of patients with thanatophoric dysplasia (TD-type I), but a lower proportion in the more prevalent achondroplasia (ACH) (ACH is primarily dominated by the G380R mutation). In reported literature, the Fgfr3*Y367C mutation is typically used to construct mouse models in a heterozygous form, which corresponds to the heterozygous nature of this mutation in human clinical patients. Its dominant-negative effect is sufficient to cause the disease ^[4]. Fgfr3-Y367C(neo-del) mice are a neo‑free disease model generated by crossing Fgfr3‑neoY367C mice (catalog No.: C001745) with Flpo mice. Internal data indicate that these double-heterozygous offspring begin to die at postnatal day 11 (P11) and exhibit typical dwarfism phenotypes, characterized by reduced overall body size, shortened long bones, craniofacial skeletal abnormalities, and decreased trunk and rib dimensions. This model can be utilized to investigate the pathogenesis and therapeutic strategies for achondroplasia (ACH) and thanatophoric dysplasia (TD).