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 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 CD19 gene encodes a member of the immunoglobulin gene superfamily. As a key co-receptor in the B cell receptor (BCR) signaling pathway, it is crucial for B cell development, activation, and differentiation. CD19, a pan-B-cell marker exclusively expressed in the B cell lineage, remains stable throughout B cell development, from pro-B cells to mature and memory B cells. It acts as a positive regulator of BCR signal transduction by forming a B cell-specific signaling complex with CD21 (complement receptor 2), CD81 (tetraspanin), and CD225 (Leu13), which lowers the threshold for antigen-induced B cell activation ^[1]. Dysregulation of CD19 is strongly linked to autoimmune diseases such as systemic lupus erythematosus (SLE) and B cell malignancies like acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma. Mutations in this gene are associated with common variable immunodeficiency 3 (CVID3), characterized by impaired B cell differentiation and hypogammaglobulinemia. Owing to its B cell-specific expression, CD19 has become a pivotal target for immunotherapy. For example, anti-CD19 CAR-T cell therapy (e.g., Tisagenlecleucel) has shown remarkable efficacy in refractory or relapsed ALL ^[2]. Recent studies have also explored CD19-targeted bispecific antibodies (e.g., blinatumomab) to enhance tumor cell clearance ^[3]. B6-hCD19 mice are a humanized model generated by replacing the mouse endogenous Cd19 gene sequence from the ATG start codon to part of intron 4 with the corresponding human CD19 gene sequence using gene editing technology. This model is applicable for studying B cell development and function, as well as therapeutic research on autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), and B cell malignancies. It is an ideal research platform for preclinical efficacy evaluation of anti-human CD19 CAR-T cell therapy, and the development of bispecific antibodies and combination therapies.

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.

The gene TNFRSF13C encodes the B cell-activating factor receptor (BAFF-R), also known as BLyS receptor 3 (BR3) or CD268. As a member of the tumor necrosis factor receptor superfamily (TNFRSF), BAFF-R functions as a crucial type III transmembrane signaling protein on lymphocytes. Its expression is predominantly observed on the surface of B cells throughout various stages of their development, from transitional to mature naive and memory populations, underscoring its vital role in peripheral B cell homeostasis ^[1]. BAFF-R serves as the primary receptor for the cytokine BAFF (TNFSF13B), and their interaction delivers essential survival and maturation signals to B cells, mediated through downstream pathways including the activation of NF-κB and PI3K. Genetic alterations in TNFRSF13C, including point mutations and deletions, or dysregulation of the BAFF-BAFF-R axis, are increasingly recognized for their contribution to immune pathology ^[2]. Such aberrations are associated with primary immunodeficiencies like common variable immunodeficiency (CVID), characterized by profound defects in antibody production and recurrent infections, as well as a range of autoimmune diseases such as systemic lupus erythematosus (SLE) and Sjögren's syndrome, and certain B cell malignancies ^[2-3]. The critical, non-redundant function of BAFF-R in B cell biology highlights its significance as a key node in adaptive immunity and positions the BAFF-BAFF-R pathway as a compelling target for therapeutic intervention in a spectrum of immune-mediated disorders. The B6-hBAFFR (hTNFRSF13C) mouse is a humanized model constructed by replacing the sequence of the mouse Tnfrsf13c endogenous extracellular domain in situ with the corresponding extracellular domain from the human TNFRSF13C. The B6-hBAFFR (hTNFRSF13C) mice can be used for the study of the pathogenesis of immune-mediated disorders such as common variable immunodeficiency (CVID), systemic lupus erythematosus (SLE), and Sjögren's syndrome, and certain B cell malignancies, as well as for TNFRSF13C-targeted drug development.

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 encodes fibroblast growth factor receptor 1 (FGFR1), a pivotal transmembrane receptor tyrosine kinase widely expressed across diverse cell types, including epithelial, mesenchymal, and neuronal lineages, playing fundamental roles in development, angiogenesis, cell proliferation, differentiation, and migration through activation of intracellular signaling cascades like MAPK/ERK, PI3K/AKT, and STAT ^[1]. Aberrant FGFR1 expression or mutations are associated with developmental syndromes and various cancers, driving tumor growth, metastasis, and therapeutic resistance; its expression is tightly regulated by diverse cellular signals ^[2]. A key splice isoform is FGFR1c, predominantly expressed in epithelial cells and characterized by a specific extracellular immunoglobulin-like domain III, conferring high-affinity binding to a subset of FGF ligands crucial for epithelial-mesenchymal interactions during development and adult tissue homeostasis ^[3]. Dysregulation of FGFR1c signaling is implicated in the pathogenesis of cancers such as breast, prostate, and lung carcinomas, contributing to tumor initiation, progression, angiogenesis, and potentially therapy resistance, highlighting the importance of understanding isoform-specific functions for targeted therapeutic interventions ^[3-4]. B6-hFGFR1c mice are humanized models generated by gene editing technology, in which the p.22R to partial intron 2 of the mouse Fgfr1 gene was replaced in situ with p.22R to 376E from the coding sequence of the human FGFR1 gene, p.377I to 823X from the coding sequence of the mouse Fgfr1 gene, and the 3'UTR of the mouse Fgfr1 gene. This model can be used to study the pathological mechanisms and therapeutic methods of cancers, metabolic diseases such as obesity, diabetes, and metabolic-associated steatohepatitis (MASH), as well as the screening and development of FGFR1c-targeted drugs, and preclinical efficacy and safety evaluations.

Cluster of Differentiation 3 (CD3) is a protein complex that acts as a co-receptor for T cells and is involved in the activation of cytotoxic T cells (CTLs) and helper T cells (THs). CD3 consists of five polypeptide chains: γ, δ, ε, ζ, and η, all of which are transmembrane proteins. The transmembrane regions of CD3 molecules connect with the transmembrane regions of TCR's two polypeptide chains through salt bridges, forming the TCR-CD3 complex, which is essential for T cell antigen recognition ^[1-2]. After TCR recognizes an antigen, the activation signal is transduced by CD3 into the T cell. CD3 is highly specific at all developmental stages of T cells, thus it is considered a T cell-specific immunohistochemical marker. Additionally, CD3 is present in almost all T cell lymphomas and leukemias and can be used to distinguish between morphologically similar B cell and bone marrow tumors. Due to its significant role in T cell activation and antigen recognition, CD3 is an important drug target in immunosuppressive therapy for type 1 diabetes and other autoimmune diseases ^[3]. The EPCAM gene encodes a transmembrane glycoprotein, Epithelial Cell Adhesion Molecule (EPCAM), also known as CD326 or Trop-1, which mediates calcium-independent homotypic cell adhesion and participates in fundamental processes including cell adhesion, migration, proliferation, and signal transduction, thereby maintaining epithelial tissue integrity ^[4]. While normally expressed on the surface of epithelial cells in organs such as the gastrointestinal tract, lungs, and skin, EPCAM is frequently overexpressed in various cancers, including colorectal, breast, and pancreatic carcinomas, but is largely absent or weakly expressed in healthy squamous epithelia ^[4]. Structurally, EPCAM comprises an extracellular domain (EpEX) mediating intercellular adhesion, a transmembrane domain, and a short intracellular domain (EpICD). Upon proteolytic cleavage by ADAM17 and γ-secretase, EpICD translocates to the nucleus, activating oncogenic pathways such as Wnt/β-catenin, ERK, and FAK-AKT, which promotes epithelial-mesenchymal transition (EMT), tumor progression, and metastasis ^[5]. Notably, EPCAM serves as a marker for circulating tumor cells (CTCs) and cancer stem cells, and its downregulation during EMT can complicate advanced cancer detection ^[5-6]. Furthermore, dysregulated EPCAM expression is associated with congenital tufting enteropathy (CTE), a severe intestinal epithelial dysfunction ^[5]. Given its involvement in tumor metastasis through interaction with HGFR (c-Met), targeting EPCAM with strategies like the neutralizing antibody EpAb2-6 in combination with HGFR inhibitors has shown promising preclinical efficacy ^[7]. The B6-hCD3/hEPCAM mouse is obtained by crossbreeding B6-hCD3 mice (Catalog No.: C001325) with B6-hEPCAM mice. It can be used for the development of CD3/EPCAM-targeted drugs, as well as for research in tumor immunotherapy and autoimmune disease-related drugs.

The CRBN gene, located on chromosome 3, exhibits broad expression across diverse tissues, including the brain, kidney, muscle, and immune cell populations such as monocytes, macrophages, dendritic cells, and B lymphocytes ^[1]. This gene encodes cereblon, a protein that functions as a key substrate receptor within the CRL4-CRBN E3 ubiquitin ligase complex. This complex mediates the ubiquitination and subsequent proteasomal degradation of specific target proteins, thereby regulating crucial cellular processes encompassing protein homeostasis, ion transport, and AMPK signaling ^[1-2]. Notably, mutations in CRBN are implicated in autosomal recessive nonsyndromic intellectual disability ^[2]. Furthermore, Cereblon protein serves as a primary molecular target for targeted protein degradation (TBD) therapy by specifically modulating the enzymatic activity of the CRL4-CRBN complex and altering its substrate recognition properties, thereby enabling the selective degradation of specific transcription factors. This molecular mechanism has emerged as a critical theoretical foundation for the clinical treatment of malignant hematological malignancies such as multiple myeloma, leading to the development of diverse therapeutic modalities including molecular glues and proteolysis targeting chimeras (PROTACs) ^[3-5]. B6-hCRBN mice are humanized models generated by gene editing technology, in which the exon 2 to partial intron 2 of the mouse Crbn gene was replaced in situ with the Exon 2~11 of the coding sequence (CDS) of human CRBN gene. This model can be used to study the pathological mechanisms and therapeutic methods of autosomal recessive nonsyndromic intellectual disability and multiple myeloma and other hematological cancers, as well as the screening, development, and preclinical efficacy and safety evaluation of CRBN-based targeted protein degradation (TBD) therapies.

The CRBN gene, located on chromosome 3, exhibits broad expression across diverse tissues, including the brain, kidney, muscle, and immune cell populations such as monocytes, macrophages, dendritic cells, and B lymphocytes ^[1]. This gene encodes cereblon, a protein that functions as a key substrate receptor within the CRL4-CRBN E3 ubiquitin ligase complex. This complex mediates the ubiquitination and subsequent proteasomal degradation of specific target proteins, thereby regulating crucial cellular processes encompassing protein homeostasis, ion transport, and AMPK signaling ^[1-2]. Notably, mutations in CRBN are implicated in autosomal recessive nonsyndromic intellectual disability ^[2]. Furthermore, Cereblon protein serves as a primary molecular target for targeted protein degradation (TBD) therapy by specifically modulating the enzymatic activity of the CRL4-CRBN complex and altering its substrate recognition properties, thereby enabling the selective degradation of specific transcription factors. This molecular mechanism has emerged as a critical theoretical foundation for the clinical treatment of malignant hematological malignancies such as multiple myeloma, leading to the development of diverse therapeutic modalities including molecular glues and proteolysis targeting chimeras (PROTACs) ^[3-5]. BALB/c-hCRBN mice are humanized models generated by gene editing technology, in which the exon 2 to partial intron 2 of the mouse Crbn gene was replaced in situ with the Exon 2~11 of the coding sequence (CDS) of human CRBN gene. This model can be used to study the pathological mechanisms and therapeutic methods of autosomal recessive nonsyndromic intellectual disability and multiple myeloma and other hematological cancers, as well as the screening, development, and preclinical efficacy and safety evaluation of CRBN-based targeted protein degradation (TBD) therapies.