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AG129
Product ID:
C001893
Strain:
129S2/SvPasCya
Status:
Description:
Interferons (IFNs) are potent cytokines that serve as a critical component of the body's first line of defense against viral infections, playing a key role in inflammation and immune control by directly inducing pathogen-inhibiting molecules that suppress viral replication [1]. Arthropod-borne viruses (arboviruses) like Dengue virus (DENV), Zika virus (ZIKV), and Yellow Fever virus (YFV) encode proteins that antagonize the IFN response, helping these viruses evade host immunity and maintain sufficient viral loads in the blood (viremia) to sustain the vector-host transmission. Arboviruses pose a significant public health threat, affecting around 3.9 billion people in tropical and subtropical regions. However, most preclinical studies suggest that arboviruses cannot inhibit IFN responses in mice, rendering immunocompetent mice resistant to infection, with low viral loads and limited circulation, thus limiting their use in infection research [2-3]. As a result, immunodeficient mouse models with defects in multiple IFN signaling pathways have become essential tools for studying arbovirus pathogenesis and vaccine development [2-4].
Studies have demonstrated that wild-type mice of strains like C57BL/6, CD-1, or 129 rarely exhibit clinical symptoms after infection with arboviruses such as ZIKV. However, the virus has been detected in the blood, ovaries, and spleen of ZIKV-infected 129 mice, suggesting that this strain may be more susceptible to arboviruses [5-6]. Because the virus can persist in the bloodstream without causing disease or death, the 129 strain can be used to evaluate the teratogenic effects of such viruses. Furthermore, the 129 strain is commonly used in interferon signaling-deficient models related to other viral infections [7-8].
The IFNAR1 gene encodes a key component of the type I IFN receptor, while the IFNGR1 gene encodes the ligand-binding chain (α) of the type II (γ) IFN receptor. AG129 mice, which are knockout models for both the type I (α/β) IFN receptor (Ifnar1) and the type II (γ) IFN receptor (Ifngr1), lack functional IFNAR1 and IFNGR1 proteins, resulting in deficiencies in α/β/γ interferon receptor signaling and heightened susceptibility to viral infections. Homozygous AG129 mice are viable and fertile, and exhibit increased sensitivity to arboviral infections, generating viremia similar to that seen in humans. Compared to IFNα/β/γR KO mice on the C57BL/6 background, the 129-background AG129 mice exhibit more pronounced neurological symptoms after infection [6,9].
Interferons (IFNs) are potent cytokines that serve as a critical component of the body's first line of defense against viral infections, playing a key role in inflammation and immune control by directly inducing pathogen-inhibiting molecules that suppress viral replication [1]. Arthropod-borne viruses (arboviruses) like Dengue virus (DENV), Zika virus (ZIKV), and Yellow Fever virus (YFV) encode proteins that antagonize the IFN response, helping these viruses evade host immunity and maintain sufficient viral loads in the blood (viremia) to sustain the vector-host transmission. Arboviruses pose a significant public health threat, affecting around 3.9 billion people in tropical and subtropical regions. However, most preclinical studies suggest that arboviruses cannot inhibit IFN responses in mice, rendering immunocompetent mice resistant to infection, with low viral loads and limited circulation, thus limiting their use in infection research [2-3]. As a result, immunodeficient mouse models with defects in multiple IFN signaling pathways have become essential tools for studying arbovirus pathogenesis and vaccine development [2-4].
Studies have demonstrated that wild-type mice of strains like C57BL/6, CD-1, or 129 rarely exhibit clinical symptoms after infection with arboviruses such as ZIKV. However, the virus has been detected in the blood, ovaries, and spleen of ZIKV-infected 129 mice, suggesting that this strain may be more susceptible to arboviruses [5-6]. Because the virus can persist in the bloodstream without causing disease or death, the 129 strain can be used to evaluate the teratogenic effects of such viruses. Furthermore, the 129 strain is commonly used in interferon signaling-deficient models related to other viral infections [7-8].
The IFNAR1 gene encodes a key component of the type I IFN receptor, while the IFNGR1 gene encodes the ligand-binding chain (α) of the type II (γ) IFN receptor. AG129 mice, which are knockout models for both the type I (α/β) IFN receptor (Ifnar1) and the type II (γ) IFN receptor (Ifngr1), lack functional IFNAR1 and IFNGR1 proteins, resulting in deficiencies in α/β/γ interferon receptor signaling and heightened susceptibility to viral infections. Homozygous AG129 mice are viable and fertile, and exhibit increased sensitivity to arboviral infections, generating viremia similar to that seen in humans. Compared to IFNα/β/γR KO mice on the C57BL/6 background, the 129-background AG129 mice exhibit more pronounced neurological symptoms after infection [6,9].
A129 (Ifnar1 KO)
Product ID:
C001891
Strain:
129S2/SvPasCya
Status:
Description:
Interferons (IFNs) are potent cytokines that serve as a critical component of the body's first line of defense against viral infections, playing a key role in inflammation and immune control by directly inducing pathogen-inhibiting molecules that suppress viral replication [1]. Arthropod-borne viruses (arboviruses) like Dengue virus (DENV), Zika virus (ZIKV), and Yellow Fever virus (YFV) encode proteins that antagonize the IFN response, helping these viruses evade host immunity and maintain sufficient viral loads in the blood (viremia) to sustain the vector-host transmission. Arboviruses pose a significant public health threat, affecting around 3.9 billion people in tropical and subtropical regions. However, most preclinical studies suggest that arboviruses cannot inhibit IFN responses in mice, rendering immunocompetent mice resistant to infection, with low viral loads and limited circulation, thus limiting their use in infection research [2-3]. As a result, immunodeficient mouse models with defects in multiple IFN signaling pathways have become essential tools for studying arbovirus pathogenesis and vaccine development [2-4].
Studies have demonstrated that wild-type mice of strains like C57BL/6, CD-1, or 129 rarely exhibit clinical symptoms after infection with arboviruses such as ZIKV. However, the virus has been detected in the blood, ovaries, and spleen of ZIKV-infected 129 mice, suggesting that this strain may be more susceptible to arboviruses [5-6]. Because the virus can persist in the bloodstream without causing disease or death, the 129 strain can be used to evaluate the teratogenic effects of such viruses. Furthermore, the 129 strain is commonly used in interferon signaling-deficient models related to other viral infections [7-8]. The IFNAR1 gene encodes a protein that is an essential component of the type I interferon (IFN) receptor, playing a critical role in the antiviral and immune responses. IFNAR1 is primarily expressed in immune cells, such as lymphocytes and dendritic cells, and various tissues, including the liver, brain, and skin. Defects in IFNAR1, whether due to mutations or regulatory abnormalities, can lead to severe diseases such as systemic lupus erythematosus, where excessive immune activation results in tissue damage, and certain cancers. Other diseases associated with IFNAR1 include hepatitis C, yellow fever, measles, papilloma, and viral infections.
The A129 (Ifnar1 KO) mice on a 129 background are a type I (α/β) interferon receptor (Ifnar1) gene knockout model. The absence of the IFNAR1 protein in these mice leads to a lack of type I IFN receptor function, thereby reducing immune response and increasing susceptibility to viral infections. Homozygous A129 (Ifnar1 KO) mice are viable and fertile, but they show increased susceptibility to arbovirus infections.
Interferons (IFNs) are potent cytokines that serve as a critical component of the body's first line of defense against viral infections, playing a key role in inflammation and immune control by directly inducing pathogen-inhibiting molecules that suppress viral replication [1]. Arthropod-borne viruses (arboviruses) like Dengue virus (DENV), Zika virus (ZIKV), and Yellow Fever virus (YFV) encode proteins that antagonize the IFN response, helping these viruses evade host immunity and maintain sufficient viral loads in the blood (viremia) to sustain the vector-host transmission. Arboviruses pose a significant public health threat, affecting around 3.9 billion people in tropical and subtropical regions. However, most preclinical studies suggest that arboviruses cannot inhibit IFN responses in mice, rendering immunocompetent mice resistant to infection, with low viral loads and limited circulation, thus limiting their use in infection research [2-3]. As a result, immunodeficient mouse models with defects in multiple IFN signaling pathways have become essential tools for studying arbovirus pathogenesis and vaccine development [2-4].
Studies have demonstrated that wild-type mice of strains like C57BL/6, CD-1, or 129 rarely exhibit clinical symptoms after infection with arboviruses such as ZIKV. However, the virus has been detected in the blood, ovaries, and spleen of ZIKV-infected 129 mice, suggesting that this strain may be more susceptible to arboviruses [5-6]. Because the virus can persist in the bloodstream without causing disease or death, the 129 strain can be used to evaluate the teratogenic effects of such viruses. Furthermore, the 129 strain is commonly used in interferon signaling-deficient models related to other viral infections [7-8]. The IFNAR1 gene encodes a protein that is an essential component of the type I interferon (IFN) receptor, playing a critical role in the antiviral and immune responses. IFNAR1 is primarily expressed in immune cells, such as lymphocytes and dendritic cells, and various tissues, including the liver, brain, and skin. Defects in IFNAR1, whether due to mutations or regulatory abnormalities, can lead to severe diseases such as systemic lupus erythematosus, where excessive immune activation results in tissue damage, and certain cancers. Other diseases associated with IFNAR1 include hepatitis C, yellow fever, measles, papilloma, and viral infections.
The A129 (Ifnar1 KO) mice on a 129 background are a type I (α/β) interferon receptor (Ifnar1) gene knockout model. The absence of the IFNAR1 protein in these mice leads to a lack of type I IFN receptor function, thereby reducing immune response and increasing susceptibility to viral infections. Homozygous A129 (Ifnar1 KO) mice are viable and fertile, but they show increased susceptibility to arbovirus infections.
B6-hITGAV
Product ID:
C001866
Strain:
C57BL/6NCya
Status:
Description:
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 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.
B6-hIL-17A
Product ID:
C001510
Strain:
C57BL/6NCya
Status:
Description:
Interleukin 17A (IL-17A) is a signature cytokine of the T helper 17 (Th17) subset of CD4+ T cells and one of the six members (IL-17A~IL-17F) of the IL-17 family. IL-17A is primarily produced by Th17 cells and can also be produced by other immune cells under certain conditions, including CD8+ T cells, γδT cells, natural killer T (NKT) cells, monocytes, neutrophils, and microglia [1]. IL-17A mediates downstream pathways that induce the production of inflammatory molecules, chemokines, antimicrobial peptides, and remodeling proteins, which have important effects on host defense, cell transport, immune regulation, and tissue repair, especially in inducing innate immune defense. In healthy skin, commensal microorganisms induce the production of IL-17A to provide antifungal protection. When the skin barrier is damaged, IL-17A promotes epithelial cell proliferation and can clear pathogenic factors, promoting tissue repair and wound healing [2]. IL-17A usually protects the body when it is acutely injured, but when a wound requires long-term healing and becomes a chronic injury, the role of IL-17A may transform into wound erosion or excessive proliferation, ultimately leading to loss of function [3].
IL-17A plays a key role in various infectious diseases, inflammations, autoimmune diseases, and cancers. Its high expression level is associated with chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, and multiple sclerosis. Lung injury caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely the result of the promotion of inflammatory reactions by cytokines such as IL-17A. Dysregulation of IL-17 signaling promotes pathogenic inflammation. IL-17A has a pathogenic role in mediating the important inflammatory pathway of psoriasis. The IL-23/Th17/IL-17A pathway is a key link in its pathogenesis, and inhibiting the expression of IL-17A can effectively alleviate psoriasis [4]. IL-17A is also associated with the course of ankylosing spondylitis (AS), and IL-17A inhibitors can effectively treat AS [5]. In addition, studies have shown that IL-17A is involved in the pathogenesis of neurodegenerative diseases in the central nervous system, and its expression level is related to the severity and progression of the disease [3].
B6-hIL-17A mice are humanized mouse models that express human IL-17A protein. They were constructed by using gene editing technology to replace the sequence encoding the endogenous extracellular domain of the mouse Il17a gene with the corresponding sequence from the human IL17A gene while retaining the mouse signal peptide. This strain can be used for mechanism research and preclinical evaluation of therapeutic drugs for various chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, and multiple sclerosis. The homozygotes are viable and fertile.
Interleukin 17A (IL-17A) is a signature cytokine of the T helper 17 (Th17) subset of CD4+ T cells and one of the six members (IL-17A~IL-17F) of the IL-17 family. IL-17A is primarily produced by Th17 cells and can also be produced by other immune cells under certain conditions, including CD8+ T cells, γδT cells, natural killer T (NKT) cells, monocytes, neutrophils, and microglia [1]. IL-17A mediates downstream pathways that induce the production of inflammatory molecules, chemokines, antimicrobial peptides, and remodeling proteins, which have important effects on host defense, cell transport, immune regulation, and tissue repair, especially in inducing innate immune defense. In healthy skin, commensal microorganisms induce the production of IL-17A to provide antifungal protection. When the skin barrier is damaged, IL-17A promotes epithelial cell proliferation and can clear pathogenic factors, promoting tissue repair and wound healing [2]. IL-17A usually protects the body when it is acutely injured, but when a wound requires long-term healing and becomes a chronic injury, the role of IL-17A may transform into wound erosion or excessive proliferation, ultimately leading to loss of function [3].
IL-17A plays a key role in various infectious diseases, inflammations, autoimmune diseases, and cancers. Its high expression level is associated with chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, and multiple sclerosis. Lung injury caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely the result of the promotion of inflammatory reactions by cytokines such as IL-17A. Dysregulation of IL-17 signaling promotes pathogenic inflammation. IL-17A has a pathogenic role in mediating the important inflammatory pathway of psoriasis. The IL-23/Th17/IL-17A pathway is a key link in its pathogenesis, and inhibiting the expression of IL-17A can effectively alleviate psoriasis [4]. IL-17A is also associated with the course of ankylosing spondylitis (AS), and IL-17A inhibitors can effectively treat AS [5]. In addition, studies have shown that IL-17A is involved in the pathogenesis of neurodegenerative diseases in the central nervous system, and its expression level is related to the severity and progression of the disease [3].
B6-hIL-17A mice are humanized mouse models that express human IL-17A protein. They were constructed by using gene editing technology to replace the sequence encoding the endogenous extracellular domain of the mouse Il17a gene with the corresponding sequence from the human IL17A gene while retaining the mouse signal peptide. This strain can be used for mechanism research and preclinical evaluation of therapeutic drugs for various chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, and multiple sclerosis. The homozygotes are viable and fertile.
B6-hPCSK9/Apoe KO
Product ID:
I001220
Strain:
C57BL/6Cya
Status:
Description:
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].
Apolipoprotein E (ApoE) is a lipid particle-associated polymorphic carrier protein encoded by the APOE gene. It is a core component of plasma lipoproteins, participating in the production, transport, and clearance of lipoproteins. ApoE is associated with chylomicrons, chylomicron remnants, high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and intermediate-density lipoprotein (IDL), especially showing preferential binding to HDL [7]. ApoE is the most important lipid transport protein in the body, having a profound impact on lipid metabolism. The interaction of ApoE with the low-density lipoprotein receptor (LDLR) is essential for the normal processing (catabolism) of triglyceride-rich lipoproteins [8]. In peripheral tissues, ApoE is primarily produced by the liver and macrophages and mediates cholesterol metabolism. In the central nervous system, ApoE is produced mainly by astrocytes and is the major cholesterol carrier in the brain. ApoE is essential for transporting cholesterol from astrocytes to neurons [7-10]. In addition, ApoE forms a complex with activated C1q, becoming a checkpoint inhibitor target of the classical complement pathway [11]. Polymorphisms of the APOE are associated with Alzheimer's disease and lipid accumulation, hyperlipidemia, atherosclerosis, high cholesterolemia, etc., and are related to the risk of various cardiovascular diseases.
The B6-hPCSK9/Apoe KO mice are obtained by crossing B6-hPCSK9 mice (Catalog No.: C001617) with B6J-Apoe KO mice (Catalog No.: C001507). B6J-Apoe KO mice exhibit elevated cholesterol levels and spontaneous atherosclerosis phenotypes due to the disruption of ApoE protein synthesis, further exacerbated under a high-fat diet (HFD). On the other hand, B6-hPCSK9 mice have the mouse Pcsk9 gene sequence replaced with the human PCSK9 gene sequence through gene editing technology, expressing the human PCSK9 protein. They can be used for the development of PCSK9-targeted drugs in hyperlipidemia, stroke, coronary heart disease, and other atherosclerotic cardiovascular diseases (ASCVD). The B6-hPCSK9/Apoe KO mice, while expressing the human PCSK9 protein, exhibit significantly elevated cholesterol levels and spontaneous atherosclerosis characteristics. These mice provide an ideal platform for the PCSK9-targeted drug development in hyperlipidemia and cardiovascular diseases, demonstrating good clinical and pathological relevance.
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].
Apolipoprotein E (ApoE) is a lipid particle-associated polymorphic carrier protein encoded by the APOE gene. It is a core component of plasma lipoproteins, participating in the production, transport, and clearance of lipoproteins. ApoE is associated with chylomicrons, chylomicron remnants, high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and intermediate-density lipoprotein (IDL), especially showing preferential binding to HDL [7]. ApoE is the most important lipid transport protein in the body, having a profound impact on lipid metabolism. The interaction of ApoE with the low-density lipoprotein receptor (LDLR) is essential for the normal processing (catabolism) of triglyceride-rich lipoproteins [8]. In peripheral tissues, ApoE is primarily produced by the liver and macrophages and mediates cholesterol metabolism. In the central nervous system, ApoE is produced mainly by astrocytes and is the major cholesterol carrier in the brain. ApoE is essential for transporting cholesterol from astrocytes to neurons [7-10]. In addition, ApoE forms a complex with activated C1q, becoming a checkpoint inhibitor target of the classical complement pathway [11]. Polymorphisms of the APOE are associated with Alzheimer's disease and lipid accumulation, hyperlipidemia, atherosclerosis, high cholesterolemia, etc., and are related to the risk of various cardiovascular diseases.
The B6-hPCSK9/Apoe KO mice are obtained by crossing B6-hPCSK9 mice (Catalog No.: C001617) with B6J-Apoe KO mice (Catalog No.: C001507). B6J-Apoe KO mice exhibit elevated cholesterol levels and spontaneous atherosclerosis phenotypes due to the disruption of ApoE protein synthesis, further exacerbated under a high-fat diet (HFD). On the other hand, B6-hPCSK9 mice have the mouse Pcsk9 gene sequence replaced with the human PCSK9 gene sequence through gene editing technology, expressing the human PCSK9 protein. They can be used for the development of PCSK9-targeted drugs in hyperlipidemia, stroke, coronary heart disease, and other atherosclerotic cardiovascular diseases (ASCVD). The B6-hPCSK9/Apoe KO mice, while expressing the human PCSK9 protein, exhibit significantly elevated cholesterol levels and spontaneous atherosclerosis characteristics. These mice provide an ideal platform for the PCSK9-targeted drug development in hyperlipidemia and cardiovascular diseases, demonstrating good clinical and pathological relevance.
B6-hIL2RA
Product ID:
C001713
Strain:
C57BL/6NCya
Status:
Description:
The interleukin-2 receptor alpha subunit, encoded by the IL2RA gene and also known as CD25, is a critical determinant of IL-2 signaling, a pathway fundamental to T cell biology. While CD25 alone exhibits low affinity for IL-2, its assembly with the IL-2 receptor beta and gamma chains forms the high-affinity receptor complex essential for robust cellular responses to this pleiotropic cytokine [1]. Expressed prominently on activated T lymphocytes, including effector and regulatory T cells, CD25 is pivotal for diverse processes such as T cell proliferation, differentiation, and the maintenance of immune tolerance, largely mediated through its indispensable role in regulatory T cell development and function [2]. Consequently, perturbations in IL2RA expression or genetic variants within the locus are strongly associated with susceptibility to a range of severe autoimmune disorders, including multiple sclerosis, type 1 diabetes, and rheumatoid arthritis, highlighting its central involvement in immune homeostasis breakdown [3]. Furthermore, aberrant CD25 expression has been observed in certain malignancies, suggesting roles beyond adaptive immunity [4]. The demonstrable impact of IL2RA on immune regulation and disease pathogenesis underscores its significance as a key molecule in immunology and a compelling target for therapeutic intervention.
The B6-hIL2RA mouse is a humanized model constructed by replacing the sequence of the mouse Il2ra endogenous extracellular domain in situ with the corresponding extracellular domain from the human IL2RA. The murine signal peptide and transmembrane-cytoplasmic region were preserved. The B6-hIL2RA mice can be used for the study of the pathogenesis of autoimmune diseases such as multiple sclerosis, type 1 diabetes, and rheumatoid arthritis, and certain malignancies, as well as for IL2RA-targeted drug development.
The interleukin-2 receptor alpha subunit, encoded by the IL2RA gene and also known as CD25, is a critical determinant of IL-2 signaling, a pathway fundamental to T cell biology. While CD25 alone exhibits low affinity for IL-2, its assembly with the IL-2 receptor beta and gamma chains forms the high-affinity receptor complex essential for robust cellular responses to this pleiotropic cytokine [1]. Expressed prominently on activated T lymphocytes, including effector and regulatory T cells, CD25 is pivotal for diverse processes such as T cell proliferation, differentiation, and the maintenance of immune tolerance, largely mediated through its indispensable role in regulatory T cell development and function [2]. Consequently, perturbations in IL2RA expression or genetic variants within the locus are strongly associated with susceptibility to a range of severe autoimmune disorders, including multiple sclerosis, type 1 diabetes, and rheumatoid arthritis, highlighting its central involvement in immune homeostasis breakdown [3]. Furthermore, aberrant CD25 expression has been observed in certain malignancies, suggesting roles beyond adaptive immunity [4]. The demonstrable impact of IL2RA on immune regulation and disease pathogenesis underscores its significance as a key molecule in immunology and a compelling target for therapeutic intervention.
The B6-hIL2RA mouse is a humanized model constructed by replacing the sequence of the mouse Il2ra endogenous extracellular domain in situ with the corresponding extracellular domain from the human IL2RA. The murine signal peptide and transmembrane-cytoplasmic region were preserved. The B6-hIL2RA mice can be used for the study of the pathogenesis of autoimmune diseases such as multiple sclerosis, type 1 diabetes, and rheumatoid arthritis, and certain malignancies, as well as for IL2RA-targeted drug development.
B6-H11-hBDCA2 (hCLEC4C)
Product ID:
C001693
Strain:
C57BL/6NCya
Status:
Description:
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].
B6-H11-hCLEC4C mice are humanized models generated by gene editing technology, in which the human CLEC4C genomic DNA was inserted at the H11 safe harbor. This modification does not affect the expression of the mouse homologous gene Clec4b1. 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.
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].
B6-H11-hCLEC4C mice are humanized models generated by gene editing technology, in which the human CLEC4C genomic DNA was inserted at the H11 safe harbor. This modification does not affect the expression of the mouse homologous gene Clec4b1. 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.
BALB/c-Zap70*W163C (SKG)
Product ID:
C001535
Strain:
BALB/cAnCya
Status:
Description:
The Zeta-chain-associated protein kinase, encoded by the ZAP70 gene, is a member of the protein tyrosine kinase family and plays a crucial role in T cell development, activation, and lymphocyte activation. Upon stimulation of the T cell antigen receptor (TCR), the ZAP70 protein is phosphorylated on tyrosine residues and, together with Src family kinases Lck and Fyn, plays a role in the initial steps of TCR-mediated signal transduction [1]. ZAP70 plays a key role in T cell signal transduction and is vital for thymocyte development. Defects in the ZAP70 protein can lead to severe combined immunodeficiency (SCID), characterized by the selective absence of CD8-positive T cells. Moreover, the expression of ZAP70 in B cells is associated with developing chronic lymphocytic leukemia (CLL) [1-2].
SKG mice are a BALB/c background strain carrying the W163C mutation in the Zap70 gene. This mutation alters the binding of the ZAP70 protein to the CD3ζ chain based on the immunoreceptor tyrosine-based activation motif (ITAM), thereby reducing TCR signal transduction and allowing autoreactive T cells to escape negative selection in the thymus and migrate to the periphery [3]. Under natural conditions or upon administration of serum complement activators, mice develop chronic autoimmune arthritis mediated by Th17 cells [4-5]. Furthermore, studies have shown that stimulation through various methods such as β-glucan or mannan can induce the disease process of rheumatoid arthritis (RA) in SKG mice, resulting in symptoms of autoimmune diseases such as ankylosing spondylitis (AS), psoriasis-like skin inflammation, RA-associated interstitial lung disease (RA-ILD), and Crohn’s disease-like ileitis [6-9].
The BALB/c-Zap70*W163C (SKG) mouse (referred to as the SKG mouse) is an autoimmune disease research model constructed by Cyagen through gene editing technology to introduce the W163C mutation into the Zap70 gene of BALB/c mice. The phenotype of this model is similar to that of the classic SKG mouse [10]. Under SPF conditions, upon triggering innate immune activation (such as β-glucan induction), it can present a variety of autoimmune disease phenotypes. Therefore, this mouse can be used for research on autoimmune diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriasis-like skin inflammation, RA-associated interstitial lung disease (RA-ILD), and Crohn’s disease-like ileitis, as well as T cell signal transduction.
The Zeta-chain-associated protein kinase, encoded by the ZAP70 gene, is a member of the protein tyrosine kinase family and plays a crucial role in T cell development, activation, and lymphocyte activation. Upon stimulation of the T cell antigen receptor (TCR), the ZAP70 protein is phosphorylated on tyrosine residues and, together with Src family kinases Lck and Fyn, plays a role in the initial steps of TCR-mediated signal transduction [1]. ZAP70 plays a key role in T cell signal transduction and is vital for thymocyte development. Defects in the ZAP70 protein can lead to severe combined immunodeficiency (SCID), characterized by the selective absence of CD8-positive T cells. Moreover, the expression of ZAP70 in B cells is associated with developing chronic lymphocytic leukemia (CLL) [1-2].
SKG mice are a BALB/c background strain carrying the W163C mutation in the Zap70 gene. This mutation alters the binding of the ZAP70 protein to the CD3ζ chain based on the immunoreceptor tyrosine-based activation motif (ITAM), thereby reducing TCR signal transduction and allowing autoreactive T cells to escape negative selection in the thymus and migrate to the periphery [3]. Under natural conditions or upon administration of serum complement activators, mice develop chronic autoimmune arthritis mediated by Th17 cells [4-5]. Furthermore, studies have shown that stimulation through various methods such as β-glucan or mannan can induce the disease process of rheumatoid arthritis (RA) in SKG mice, resulting in symptoms of autoimmune diseases such as ankylosing spondylitis (AS), psoriasis-like skin inflammation, RA-associated interstitial lung disease (RA-ILD), and Crohn’s disease-like ileitis [6-9].
The BALB/c-Zap70*W163C (SKG) mouse (referred to as the SKG mouse) is an autoimmune disease research model constructed by Cyagen through gene editing technology to introduce the W163C mutation into the Zap70 gene of BALB/c mice. The phenotype of this model is similar to that of the classic SKG mouse [10]. Under SPF conditions, upon triggering innate immune activation (such as β-glucan induction), it can present a variety of autoimmune disease phenotypes. Therefore, this mouse can be used for research on autoimmune diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriasis-like skin inflammation, RA-associated interstitial lung disease (RA-ILD), and Crohn’s disease-like ileitis, as well as T cell signal transduction.
B6-hLPA(CKI)/Alb-cre/hPCSK9
Product ID:
I002079
Strain:
C57BL/6NCya
Status:
Description:
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 (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).
B6-hPD-1/hCTLA4
Product ID:
I001143
Strain:
C57BL/6NCya
Status:
Description:
PD-1 and CTLA-4 are checkpoint receptors that critically modulate T cell immunity. The genes PDCD1 and CTLA4 encode PD-1 and CTLA-4 respectively, with CTLA4 expression largely restricted to T cells, while PDCD1 is evident in activated T cells, B cells, and myeloid populations [1]. These transmembrane proteins function as key negative regulators of T cell activation [2]. CTLA-4 primarily operates in lymphoid tissues during early immune responses to restrain T cell proliferation, whereas PD-1 predominantly acts in peripheral tissues during the effector phase to dampen T cell activity and limit immunopathology, particularly in chronically stimulated or ‘exhausted’ T cells [2-3]. Aberrant regulation of PD-1 and CTLA-4 is implicated in the pathogenesis of cancers, including melanoma, non-small cell lung cancer, and renal cell carcinoma, as well as chronic viral infections such as hepatitis B and C [1][4]. Clinically, monoclonal antibodies targeting CTLA-4 (e.g., ipilimumab) and PD-1 (e.g., nivolumab, pembrolizumab) are established immunotherapeutic agents that enhance anti-tumor responses. By blocking these negative signaling pathways, these monoclonal antibodies restore the anti-tumor activity of T cells, significantly enhancing anti-tumor responses [1-2]. These drug applications have not only improved the treatment outcomes for various cancers but also offer new strategies for the treatment of chronic viral infections.
B6-hPD-1/hCTLA4 mouse is a dual humanized model of PD1 and CTLA4 constructed by humanizing the mouse Pdcd1 gene based on the CTLA4 humanized mouse model (Catalog No. C001413), due to the fact that the mouse Pdcd1 gene and Ctla4 gene are on the same chromosome. These mice express human CTLA4 and PDCD1 genomic sequences under the control of mouse promoters. This model is capable of reproducing the human PD-1/CTLA4 signaling pathway and is a valuable tool for studying cancers and chronic viral infections. Furthermore, this model provides a powerful preclinical research platform for evaluating the efficacy and mechanism of therapeutic drugs targeting the PD-1/CTLA4 signaling pathway.
PD-1 and CTLA-4 are checkpoint receptors that critically modulate T cell immunity. The genes PDCD1 and CTLA4 encode PD-1 and CTLA-4 respectively, with CTLA4 expression largely restricted to T cells, while PDCD1 is evident in activated T cells, B cells, and myeloid populations [1]. These transmembrane proteins function as key negative regulators of T cell activation [2]. CTLA-4 primarily operates in lymphoid tissues during early immune responses to restrain T cell proliferation, whereas PD-1 predominantly acts in peripheral tissues during the effector phase to dampen T cell activity and limit immunopathology, particularly in chronically stimulated or ‘exhausted’ T cells [2-3]. Aberrant regulation of PD-1 and CTLA-4 is implicated in the pathogenesis of cancers, including melanoma, non-small cell lung cancer, and renal cell carcinoma, as well as chronic viral infections such as hepatitis B and C [1][4]. Clinically, monoclonal antibodies targeting CTLA-4 (e.g., ipilimumab) and PD-1 (e.g., nivolumab, pembrolizumab) are established immunotherapeutic agents that enhance anti-tumor responses. By blocking these negative signaling pathways, these monoclonal antibodies restore the anti-tumor activity of T cells, significantly enhancing anti-tumor responses [1-2]. These drug applications have not only improved the treatment outcomes for various cancers but also offer new strategies for the treatment of chronic viral infections.
B6-hPD-1/hCTLA4 mouse is a dual humanized model of PD1 and CTLA4 constructed by humanizing the mouse Pdcd1 gene based on the CTLA4 humanized mouse model (Catalog No. C001413), due to the fact that the mouse Pdcd1 gene and Ctla4 gene are on the same chromosome. These mice express human CTLA4 and PDCD1 genomic sequences under the control of mouse promoters. This model is capable of reproducing the human PD-1/CTLA4 signaling pathway and is a valuable tool for studying cancers and chronic viral infections. Furthermore, this model provides a powerful preclinical research platform for evaluating the efficacy and mechanism of therapeutic drugs targeting the PD-1/CTLA4 signaling pathway.
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