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 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 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 SLC16A1 gene encodes the Monocarboxylate Transporter 1 (MCT1) protein, a vital proton-coupled symporter that facilitates the rapid transmembrane movement of metabolic substrates, including lactate, pyruvate, and ketone bodies (acetoacetate and β-hydroxybutyrate). This gene is ubiquitously expressed across nearly all human tissues to maintain energy balance and pH homeostasis, with notably high levels labeled in the heart, oxidative skeletal muscle fibers, erythrocytes (red blood cells), and the brain (specifically in oligodendrocytes and the blood-brain barrier), while being uniquely "disallowed" or suppressed in normal pancreatic beta-cells to prevent inappropriate insulin release ^[1]. Functionally, MCT1 is central to the "lactate shuttle" mechanism, allowing tissues to coordinate metabolic fuel exchange by facilitating either the influx or efflux of substrates depending on the concentration gradient and proton motive force ^[2]. Mutations in SLC16A1 are clinically linked to Erythrocyte Lactate Transporter Defect, which causes exercise-induced muscle cramping and fatigue, and Monocarboxylate Transporter 1 Deficiency, a rare disorder characterized by recurrent episodes of severe ketoacidosis and vomiting triggered by fasting or infection ^[3]. Conversely, gain-of-function mutations in the gene's promoter lead to familial hyperinsulinemia type 7 (HHF7), where exercise triggers excessive insulin secretion, while its widespread overexpression in various cancers (such as melanoma and lung cancer) supports the Warburg effect by managing lactate efflux to prevent intracellular acidification and fueling tumor progression ^[4]. The B6-huSLC16A1 mouse is a humanized model constructed through gene-editing technology, in which the sequences from the ATG start codon to the TGA stop codon of the endogenous mouse Slc16a1 gene are replaced with the sequences from the ATG start codon to the TGA stop codon of the human SLC16A1 gene. This model can be used for research on diseases such as Erythrocyte Lactate Transporter Defect, Monocarboxylate Transporter 1 Deficiency, familial hyperinsulinemia type 7 (HHF7), and various cancers, as well as for screening, development, and preclinical evaluation of SLC16A1-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.

The B6-huCFTR*F508del/huHER2 mouse is a humanized disease model obtained by mating B6-huCFTR*F508del mice (catalog No.: I001226) with B6-huHER2 (huERBB2) mice (catalog No.: C001627). ^b Homozygous B6-huCFTR*F508del mice need to be fed with intestinal cleansers after 3 weeks of age to maintain their survival.^/b This model can be used for research on the pathological mechanisms and treatment methods of cystic fibrosis (CF) and cancer, as well as for the development of CFTR/HER2-targeted drugs.

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.

The B6-huIL4/huIL13/huTSLP mouse is a triple-gene humanized model obtained by mating B6-huIL4 mice (catalog number: C001628), B6-huIL13 mice (catalog number: C001634), and B6-huTSLP mice (catalog number: C001809). This model can be used for the mechanism research and development of treatment methods in allergic diseases, inflammation and autoimmune diseases, Th2 immune response, parasitic infections, tumor immunology, as well as the development of IL-4/IL13/TSLP-targeted drugs, and the pre-clinical evaluation of drug efficacy and safety.

The B6-hAGT/hREN/huPCSK9 mouse is a humanized model obtained by mating the hREN x hAGT mouse (catalog No.: C001336) with the B6-huPCSK9 mouse (catalog No.: C001617). This model can be used for mechanism research on chronic hypertension, various metabolic diseases, neurodegenerative diseases, and tumorigenesis, as well as the development of relevant treatment methods.

Proprotein convertase subtilisin/kexin 9 (PCSK9) is a serine protease primarily produced in the liver but expressed in other tissues, including the intestine, heart, and neurons. The N-terminal domain of the PCSK9 protein is responsible for protein localization and stability, while the C-terminal domain is responsible for protein enzymatic activity ^[1]. The Low-density lipoprotein receptor (LDLR) is a receptor that is responsible for clearing low-density lipoprotein cholesterol (LDL-C) from the blood. PCSK9 cleaves the intracellular domain of LDLR on the cell surface, causing it to detach from the cell membrane and be transported to the lysosome for degradation, promoting LDLR degradation, and increasing plasma LDL-C. Overexpression or gain-of-function mutations of the PCSK9 gene can lead to LDL-C accumulation by reducing LDLR levels. This can cause hypercholesterolemia, which increases the risk of cardiovascular diseases, such as atherosclerosis and coronary heart disease, and neurodegenerative diseases, such as Alzheimer's disease ^[2]. PCSK9 has become an important target for the development of lipid-lowering drugs. Several PCSK9-targeted antibodies or small nucleic acid drugs have been approved for marketing worldwide, including evolocumab from Amgen, alirocumab from Sanofi and Regeneron, and inclisiran from Novartis. These drugs primarily work by inhibiting PCSK9 activity or preventing PCSK9 protein from binding to LDLR, lowering LDL-C levels in the blood to treat hypercholesterolemia ^[3-4]. In addition, PCSK9 can promote tumor growth and development by regulating cell proliferation, migration, and invasion. It can also regulate the expression of inflammatory factors that contribute to inflammation. Therefore, targeting the expression of PCSK9 has been investigated in tumor immunotherapy and autoimmune disease therapy ^[5-6]. B6-hPCSK9 mice are a humanized model generated by gene editing technology to replace the mouse Pcsk9 gene with the human PCSK9 gene sequence. These mice express human PCSK9 protein and can be used for research on various metabolic diseases, neurodegenerative diseases, tumor development, autoimmune disease mechanisms, and for the preclinical pharmacological evaluation of PCSK9-targeted drugs. In addition, Cyagen has developed a similar model, the B6-hPCSK9(CDS) mouse (PCSK9 coding sequence humanized model, Catalog Number: C001593). Compared to the B6-hPCSK9 mouse model, the B6-hPCSK9(CDS) mouse expresses higher levels of human PCSK9 and exhibits LDLR protein expression closer to physiological levels. It is recommended to choose the appropriate model based on the type of drug or research direction.