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 Transferrin receptor (TFRC) gene encodes Transferrin Receptor 1 (TFR1), a protein that is expressed at low levels in most normal cells but shows increased expression in highly proliferative cells, such as basal epidermal cells, intestinal epithelium, and certain activated immune cells. Brain capillary endothelial cells, which constitute the blood-brain barrier (BBB), also express this receptor at high levels ^[1]. TFR1 plays a critical role in maintaining iron metabolism and homeostasis by facilitating receptor-mediated endocytosis of iron-bound transferrin (Tf) via Tf cycling, thereby promoting iron uptake ^[2]. Cellular iron deficiency can lead to apoptosis, while cellular transformation requires substantial iron to sustain proliferation, with iron overload contributing to tumor progression. The high expression of TFR1 in many tumors makes it a potential tumor marker, offering a target for therapies to inhibit tumor growth and metastasis ^[1]. Moreover, TFR1 is implicated in anemia and iron metabolism disorders. Studies have shown that elevated TFR1 expression in cardiomyocytes is associated with exacerbated inflammation in myocarditis patients ^[3]. As a target for antibody-mediated cancer therapy, TFR1 can be leveraged through two approaches: one involves the use of antibodies conjugated to anti-cancer drugs, which are indirectly internalized via receptor-mediated endocytosis; the other employs antibodies that directly disrupt receptor function or induce Fc effector functions such as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or complement-dependent cytotoxicity (CDC). Various clinical drugs targeting TFR1 are currently under development, including antisense oligonucleotides (ASOs), antibody-drug conjugates (ADCs), and antibody-oligonucleotide conjugates, applicable to diseases such as cancer, anemia, and neurodegenerative disorders. Research indicates that enhancing antibody transport across the blood-brain barrier via TFR1, by forming specific bispecific antibodies with anti-β-amyloid antibodies, can improve therapeutic outcomes in Alzheimer's patients ^[4-5]. As research progresses, TFR1 is expected to become an effective clinical target for multiple diseases and a synergistic target for drug delivery across the blood-brain barrier (BBB). The B6-hTFRC (CDS) mouse model was generated by inserting the human TFRC gene sequence into the mouse Tfrc gene locus using gene-editing technology. To minimize interference from mouse gene sequences or proteins, part of the mouse Tfrc gene sequence was knocked out, resulting in a model expressing only the human TFR1 protein. This model is valuable for studying iron metabolism disorders, neurodegenerative diseases, and tumor development, supporting the development of TFR1-targeted therapeutics and preclinical pharmacological evaluations.

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.

Lipoprotein A (LPA) is a type of particle similar to low-density lipoprotein (LDL) that is considered one of the risk factors for cardiovascular disease (CVD), such as atherosclerosis, coronary heart disease, stroke, etc ^[1]. LP(a) is similar in size and lipid content to LDL (low-density lipoprotein) and also contains the lipoprotein ApoB-100. However, unlike LDL, LP(a) additionally contains a variable-length lipoprotein called Apo(a), which covalently binds to ApoB-100 through a single disulfide bond. LP(a) plays an important role in systemic lipid transport, guiding inflammatory cells into blood vessel walls and leading to smooth muscle cell proliferation. Furthermore, it is involved in wound healing and tissue repair, interacting with the components of blood vessel walls and the extracellular matrix ^[2]. However, LP(a) can also cause arterial narrowing by adhering to the arterial wall, accelerating the formation of blood clots, and thereby triggering a series of pathological changes related to coronary heart disease, cardiovascular disease, atherosclerosis, thrombus formation, and stroke ^[3]. The plasma concentration of LP(a) is closely related to genetic factors and is primarily regulated by the LPA gene. Therefore, the LPA gene is an important potential target for cardiovascular disease treatment. The LPA gene encodes a serine protease that inhibits the activity of tissue-type plasminogen activator I. Fragments of this protein, generated through protein hydrolysis, can adhere to atherosclerotic lesions in arteries, promoting blood clot formation. The LPA gene is expressed in both humans and non-human primates but is not expressed in mice. Constructing mouse models expressing the human LPA gene is of significant importance for developing lipid-lowering drugs, which can drive the development of novel therapies for cardiovascular diseases. Currently, various novel therapies targeting the transcription rate of the LPA gene are under development, including small interfering RNA (siRNA) and antisense oligonucleotides (ASO) ^[4]. This strain was generated by mating B6-hLPA(CKI) mice (catalog number: C001521) with Alb-Cre mice (liver-specific Cre-expressing mice), resulting in a mouse model with liver-specific overexpression of the human LPA gene. B6-hLPA(CKI)/Alb-cre mice can be used to study the relationship between the LPA gene and hyperlipidemia and related cardiovascular diseases.

Lipoprotein A (LPA) is a type of particle similar to low-density lipoprotein (LDL) that is considered one of the risk factors for cardiovascular disease (CVD), such as atherosclerosis, coronary heart disease, stroke, etc ^[1]. LP(a) is similar in size and lipid content to LDL (low-density lipoprotein) and also contains the lipoprotein ApoB-100. However, unlike LDL, LP(a) additionally contains a variable-length lipoprotein called Apo(a), which covalently binds to ApoB-100 through a single disulfide bond. LP(a) plays an important role in systemic lipid transport, guiding inflammatory cells into blood vessel walls and leading to smooth muscle cell proliferation. Furthermore, it is involved in wound healing and tissue repair, interacting with the components of blood vessel walls and the extracellular matrix ^[2]. However, LP(a) can also cause arterial narrowing by adhering to the arterial wall, accelerating the formation of blood clots, and thereby triggering a series of pathological changes related to coronary heart disease, cardiovascular disease, atherosclerosis, thrombus formation, and stroke ^[3]. The plasma concentration of LP(a) is closely related to genetic factors and is primarily regulated by the LPA gene. Therefore, the LPA gene is an important potential target for cardiovascular disease treatment. The LPA gene encodes a serine protease that inhibits the activity of tissue-type plasminogen activator I. Fragments of this protein, generated through protein hydrolysis, can adhere to atherosclerotic lesions in arteries, promoting blood clot formation. The LPA gene is expressed in both humans and non-human primates but is not expressed in mice. Constructing mouse models expressing the human LPA gene is of significant importance for developing lipid-lowering drugs, which can drive the development of novel therapies for cardiovascular diseases. Currently, various novel therapies targeting the transcription rate of the LPA gene are under development, including small interfering RNA (siRNA) and antisense oligonucleotides (ASO) ^[4]. 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 ^[5]. 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 ^[6]. PCSK9 has emerged as a key 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 ^[7-8]. 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 ^[9-10]. The B6-hLPA (CKI)/Alb-cre/hPCSK9 mouse model is generated by crossing B6-hLPA (CKI) mice (Catalog No.: C001521, a mouse strain with conditional expression of the human LPA gene), Alb-Cre mice (liver-specific Cre-expressing mice), and B6-hPCSK9 mice (Catalog No.: C001617). This model harbors two cardiovascular disease risk factors, namely Lp (a) (lipoprotein (a)) and PCSK9, making it suitable for research on hyperlipidemia, stroke, coronary heart disease, and other atherosclerotic cardiovascular diseases (ASCVD).

Lipoprotein(a) (LP(a)) is considered one of the risk factors for atherosclerosis, coronary heart disease, stroke, and other cardiovascular diseases (CVD) ^[1]. It is similar in size and lipid content to low-density lipoprotein (LDL) and contains the lipoprotein ApoB-100, but also includes a variable-length lipoprotein(a) (Apo(a)), which is covalently bound to ApoB-100 via a single disulfide bond. LP(a) plays an important role in systemic lipid transport, guiding inflammatory cells into the vascular wall and causing smooth muscle cell proliferation. In addition, it is also involved in wound healing and tissue repair, interacting with components of the vascular wall and extracellular matrix ^[2]. LP(a) can also cause arterial narrowing by attaching to the arterial wall, accelerating the formation of blood clots, and leading to a series of pathological changes ^[3]. The plasma concentration of LP(a) is closely related to genetic factors and is mainly regulated by the LPA gene. Therefore, the LPA gene is an important potential target for treating cardiovascular disease. The LPA gene is expressed in humans and non-human primates but not mice. By crossing mice conditional expression of human LPA (LSL-hLPA) with liver-specific Cre expression mice (Alb-Cre) that specifically overexpress the human LPA gene in the liver can be obtained. ApoB is a protein that plays a central role in lipid metabolism and cardiovascular disease (CVD) and is responsible for transporting cholesterol and other fat molecules to all tissues throughout the body ^[4]. The accumulation of cholesterol and other lipids can promote the formation of arterial plaques, leading to arterial narrowing and reduced blood flow, increasing the risk of cardiovascular events such as myocardial infarction and stroke ^[5]. Therefore, high levels of ApoB are a major risk factor for plaque in cardiovascular diseases such as atherosclerosis. ApoB100 is the most abundant subtype of ApoB in humans and the most important subtype of ApoB in cardiovascular disease (CVD) ^[6]. Mice overexpressing the human APOB gene have significantly elevated LDL cholesterol in serum. The B6-RCL-hLPA/Alb-cre/TG(APOB) mice express human LP(a) and ApoB, two risk factors for cardiovascular disease. It can be used in the study of hyperlipidemia, stroke, coronary heart disease, familial hypercholesterolemia (FH), and other atherosclerotic cardiovascular diseases (ASCVD). Internal data (not shown) indicates that, compared to the Cyagen strain B6-LPA(CKI)/Alb-Cre&Tg(APOB) mice (Catalog No. C001494), this model exhibits a more stable expression of human LPA protein at different ages. Please choose the model based on the experimental need for continuous stability of human LPA protein expression.

Asialoglycoprotein receptor 1 (ASGR1), encoded by the ASGR1 gene, is central to cholesterol homeostasis and liver pathophysiology. Primarily localized to the hepatocyte plasma membrane, ASGR1 mediates ligand internalization and lysosomal degradation ^[1-2]. Ligand binding triggers ASGR1-dependent metabolism, involving the formation of a heteromeric complex with ASGR2, which recognizes glycoproteins with terminal galactose or N-acetylgalactosamine residues. Through modulation of the liver X receptor (LXR)/breast cancer susceptibility gene 1 (BRCA1)/BRCA1-associated ring domain protein 1 (BARD1) pathway, ASGR1 facilitates cholesterol excretion into bile, thereby influencing systemic lipid levels ^[1-2]. Beyond cholesterol regulation, ASGR1 participates in liver lesion processes, underscoring its broader role in liver health ^[3]. Notably, loss-of-function mutations in ASGR1 correlate with reduced circulating cholesterol and decreased cardiovascular disease risk. Conversely, elevated serum soluble ASGR1 (sASGR1) levels are associated with increased low-density lipoprotein cholesterol (LDL-C), particularly in hypertensive individuals ^[3]. Consequently, ASGR1 has emerged as a therapeutic target for cardiovascular and hepatic disorders, including hypercholesterolemia, atherosclerosis, non-alcoholic fatty liver disease, and cirrhosis ^[2-4]. The B6-huASGR1 mouse model was generated by replacing sequences from the ATG start codon to the TAG stop codon of the endogenous mouse Asgr1 gene with the sequences from the ATG start codon to the TAA stop codon of the human ASGR1 gene. This model can be used to study the pathological mechanisms and therapeutic approaches for cardiovascular and liver diseases, as well as for the development of ASGR1-targeted drugs.

The TNFRSF13B gene encodes the transmembrane activator and CAML interactor (TACI), a receptor belonging to the tumor necrosis factor receptor superfamily, predominantly expressed on B lymphocytes. TACI plays a critical role in humoral immunity by recognizing the TNF ligands B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) ^[1]. Upon ligand binding, TACI modulates intracellular signaling pathways, including NFAT, AP1, and NF-κB, which are essential for B cell survival, maturation into plasma cells, and the production of immunoglobulins ^[2]. Notably, TNFRSF13B is highly polymorphic, and specific genetic variants are strongly associated with the pathogenesis of common variable immunodeficiency (CVID), a primary immunodeficiency characterized by hypogammaglobulinemia and increased susceptibility to infection ^[3]. While the precise mechanisms by which these variants contribute to disease are still under investigation, they often result in impaired TACI function, disrupting normal B cell development and antibody responses ^[4]. Further research into the regulation and function of TACI is crucial for understanding the complex etiology of CVID and for developing targeted therapeutic strategies for this and potentially other immune-related disorders. The B6-hTNFRSF13B mouse is a humanized model constructed by replacing the exon 2 plus partial intron 2 of the mouse Tnfrsf13b gene in situ with the "Kozak-TNFRSF13B chimeric CDS-3'UTR of mouse Tnfrsf13b-WPRE-BGH pA" cassette. The B6-hTNFRSF13B mice can be used for studies on common variable immunodeficiency (CVID), and pathogenesis of immune-related diseases, as well as for TNFRSF13B-targeted drug development.

The CLEC4C gene, also known as BDCA-2 or CD303, encodes a type II transmembrane C-type lectin receptor predominantly expressed by plasmacytoid dendritic cells (pDCs) ^[1]. This receptor plays a critical role in pDC biology and serves as a key marker for this cell type ^[2]. The CLEC4C protein, featuring a carbohydrate recognition domain, is implicated in the capture and subsequent processing of antigens, potentially through the recognition of specific glycans and immunoglobulin G ^[1]. Functionally, CLEC4C acts as a signaling receptor within pDCs, and its engagement can negatively regulate the production of type I interferons, thereby modulating immune responses ^[2]. Notably, dysregulation of CLEC4C expression and pDC function has been associated with the pathogenesis of autoimmune disorders, including systemic lupus erythematosus (SLE), as well as in the context of certain hematological malignancies ^[3]. Litifilimab is a monoclonal antibody that targets CLEC4C and is under investigation for the treatment of SLE and other interferonopathies ^[4]. CLEC4C is a human gene, while Clec4b1 is its orthologous gene in mice. The B6-hCLEC4C mouse is a humanized model constructed by replacing the mouse Clec4b1 endogenous extracellular domain with the human CLEC4C extracellular domain. This model can be used to study the pathological mechanisms and therapeutic methods of autoimmune disorders and hematological malignancies, as well as the screening and development of CLEC4C-targeted drugs, and preclinical efficacy and safety evaluations.