필터
에 대한 검색 결과 163 건
정렬 기준:
알파벳순 (A-Z)
베스트셀러
AG129
제품 ID:
C001893
계통(Strain):
129S2/SvPasCya
상태:
설명:
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)
제품 ID:
C001891
계통(Strain):
129S2/SvPasCya
상태:
설명:
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-hPCSK9/Apoe KO
제품 ID:
I001220
계통(Strain):
C57BL/6Cya
상태:
설명:
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
제품 ID:
C001713
계통(Strain):
C57BL/6NCya
상태:
설명:
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)
제품 ID:
C001693
계통(Strain):
C57BL/6NCya
상태:
설명:
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)
제품 ID:
C001535
계통(Strain):
BALB/cAnCya
상태:
설명:
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
제품 ID:
I002079
계통(Strain):
C57BL/6NCya
상태:
설명:
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
제품 ID:
I001143
계통(Strain):
C57BL/6NCya
상태:
설명:
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.
B6-hTL1A/hIL23A
제품 ID:
C001837
계통(Strain):
C57BL/6N;6JCya
상태:
설명:
TNF-like ligand 1A (TL1A), also known as TNF superfamily member 15 (TNFSF15), is a member of the tumor necrosis factor (TNF) family encoded by the TNFSF15 gene in humans. TL1A acts as a ligand for death receptor 3 (DR3) and decoy receptor 3 (DcR3), providing a stimulatory signal for downstream pathways. It regulates the proliferation, activation, and apoptosis of effector cells, as well as cytokine and chemokine production. TL1A is expressed in various immune cells, including monocytes, macrophages, dendritic cells, and T cells, as well as in non-immune cells such as synovial fibroblasts and endothelial cells. It plays a crucial role in modulating immune responses by promoting the differentiation and survival of T cells, particularly Th17 cells involved in inflammatory processes [1]. TL1A enhances IL-2 responses in anti-CD3/CD28-stimulated T cells and synergizes with IL-12 and IL-18 to augment IFN-γ release in human T and NK cells, biasing T cell differentiation toward a Th1 phenotype [2]. Dysregulation of TL1A expression is implicated in autoimmune diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), primary biliary cholangitis (PBC), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS) [1]. TL1A has emerged as a promising therapeutic target, with ongoing research focused on developing monoclonal antibodies and other biologics to neutralize TL1A and reduce inflammation in autoimmune disorders. Clinical trial results suggest that TL1A inhibition can be used in the treatment of various autoimmune diseases, particularly IBD [3-5].
The IL23A gene encodes the p19 subunit, a component of interleukin-23 (IL-23), which forms a heterodimer with the p40 subunit (encoded by IL12B) to generate the functional IL-23 cytokine [1]. Primarily expressed by activated dendritic cells, macrophages, and monocytes, IL-23 signals through the IL-23 receptor (IL-23R) complex, activating the JAK-STAT pathway to promote Th17 cell differentiation and maintain IL-17 production. This process drives inflammatory responses and mucosal immunity against extracellular pathogens [6-7]. Genetic polymorphisms within IL23A are strongly associated with autoimmune and inflammatory diseases, including psoriasis, Crohn's disease, and inflammatory bowel disease, due to dysregulated Th17 activity and chronic inflammation [6-7]. Monoclonal antibodies targeting IL-23, such as risankizumab and guselkumab, selectively block the p19 subunit, demonstrating therapeutic efficacy in psoriasis and inflammatory bowel diseases by suppressing pathogenic IL-17/Th17 pathways [8]. While IL-23 plays a role in protective immunity, its overactivation contributes to tissue damage in autoimmune settings, highlighting its dual function in immune regulation and disease pathogenesis [6-9].
B6-hTL1A/hIL23A mice are humanized models generated by crossing B6-hTL1A (TNFSF15) mice (Catalog No.: C001603) with B6-hIL23A mice (Catalog No.: C001618). These mice are suitable for studying the pathological mechanisms and therapeutic strategies of allergic and inflammatory diseases, immune-related disorders, and cancer, as well as for the screening, development, and preclinical evaluation of TL1A/IL23A-targeted drugs.
TNF-like ligand 1A (TL1A), also known as TNF superfamily member 15 (TNFSF15), is a member of the tumor necrosis factor (TNF) family encoded by the TNFSF15 gene in humans. TL1A acts as a ligand for death receptor 3 (DR3) and decoy receptor 3 (DcR3), providing a stimulatory signal for downstream pathways. It regulates the proliferation, activation, and apoptosis of effector cells, as well as cytokine and chemokine production. TL1A is expressed in various immune cells, including monocytes, macrophages, dendritic cells, and T cells, as well as in non-immune cells such as synovial fibroblasts and endothelial cells. It plays a crucial role in modulating immune responses by promoting the differentiation and survival of T cells, particularly Th17 cells involved in inflammatory processes [1]. TL1A enhances IL-2 responses in anti-CD3/CD28-stimulated T cells and synergizes with IL-12 and IL-18 to augment IFN-γ release in human T and NK cells, biasing T cell differentiation toward a Th1 phenotype [2]. Dysregulation of TL1A expression is implicated in autoimmune diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), primary biliary cholangitis (PBC), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS) [1]. TL1A has emerged as a promising therapeutic target, with ongoing research focused on developing monoclonal antibodies and other biologics to neutralize TL1A and reduce inflammation in autoimmune disorders. Clinical trial results suggest that TL1A inhibition can be used in the treatment of various autoimmune diseases, particularly IBD [3-5].
The IL23A gene encodes the p19 subunit, a component of interleukin-23 (IL-23), which forms a heterodimer with the p40 subunit (encoded by IL12B) to generate the functional IL-23 cytokine [1]. Primarily expressed by activated dendritic cells, macrophages, and monocytes, IL-23 signals through the IL-23 receptor (IL-23R) complex, activating the JAK-STAT pathway to promote Th17 cell differentiation and maintain IL-17 production. This process drives inflammatory responses and mucosal immunity against extracellular pathogens [6-7]. Genetic polymorphisms within IL23A are strongly associated with autoimmune and inflammatory diseases, including psoriasis, Crohn's disease, and inflammatory bowel disease, due to dysregulated Th17 activity and chronic inflammation [6-7]. Monoclonal antibodies targeting IL-23, such as risankizumab and guselkumab, selectively block the p19 subunit, demonstrating therapeutic efficacy in psoriasis and inflammatory bowel diseases by suppressing pathogenic IL-17/Th17 pathways [8]. While IL-23 plays a role in protective immunity, its overactivation contributes to tissue damage in autoimmune settings, highlighting its dual function in immune regulation and disease pathogenesis [6-9].
B6-hTL1A/hIL23A mice are humanized models generated by crossing B6-hTL1A (TNFSF15) mice (Catalog No.: C001603) with B6-hIL23A mice (Catalog No.: C001618). These mice are suitable for studying the pathological mechanisms and therapeutic strategies of allergic and inflammatory diseases, immune-related disorders, and cancer, as well as for the screening, development, and preclinical evaluation of TL1A/IL23A-targeted drugs.
B6-hCD40/hCD40LG
제품 ID:
C001781
계통(Strain):
C57BL/6NCya
상태:
설명:
The CD40 gene encodes CD40, a transmembrane protein belonging to the tumor necrosis factor receptor (TNFR) superfamily. Primarily expressed on antigen-presenting cells (APCs) such as B lymphocytes, macrophages, and dendritic cells, CD40 is also found on a variety of non-immune cells including endothelial cells, fibroblasts, epithelial cells, and smooth muscle cells, as well as many tumor cells [1]. The CD40LG gene is located on the X chromosome (Xq26.3) and encodes CD40 ligand (CD40L, also known as CD154), a type II transmembrane protein mainly expressed on activated T cells, platelets, and some B cells. Under inflammatory conditions, monocytes, natural killer cells, mast cells, and basophils can also be induced to express CD40L [2-4].
The interaction of CD40 with its ligand, CD40L (CD154), is a critical costimulatory signal essential for T-dependent humoral and cell-mediated immunity. This interaction triggers downstream signaling pathways, including NF-κB, JNK, and JAK/STAT, leading to B cell activation, proliferation, differentiation, isotype switching, memory B cell development, germinal center formation, and enhanced APC function and cytokine production [5]. Dysregulation of CD40/CD40L signaling pathway is implicated in the pathogenesis of numerous diseases, including autoimmune disorders like inflammatory bowel disease (IBD), type 1 diabetes (T1D), multiple sclerosis, and rheumatoid arthritis (RA), as well as cardiovascular diseases such as atherosclerosis, certain neurological conditions including Alzheimer's disease (AD) and traumatic brain injury, and various cancers [5-7].
Due to the important role of the CD40/CD40L interaction in immune activation, CD40/CD40L has been an important target for immunotherapy. In recent years, significant progress has been made in CD40/CD40L-targeted therapy. Various drugs have been developed, including agonistic/antagonistic monoclonal antibodies, cellular vaccines, adenoviral vectors, and protein antagonists, and have shown therapeutic potential in malignant tumors, autoimmune diseases, and allograft rejection [1].
The B6-hCD40/hCD40LG mouse is a dual-gene humanized model (for CD40 and CD40LG) generated by crossing B6-hCD40 mice (Catalog No.: C001721) with B6-hCD40LG mice (Catalog No.: C001720). The B6-hCD40/hCD40LG mouse model can be used for research on the mechanisms and therapeutic approaches of diseases such as autoimmune diseases, cancer, and cardiovascular diseases, as well as for the development of CD40/CD40L-targeted drugs.
The CD40 gene encodes CD40, a transmembrane protein belonging to the tumor necrosis factor receptor (TNFR) superfamily. Primarily expressed on antigen-presenting cells (APCs) such as B lymphocytes, macrophages, and dendritic cells, CD40 is also found on a variety of non-immune cells including endothelial cells, fibroblasts, epithelial cells, and smooth muscle cells, as well as many tumor cells [1]. The CD40LG gene is located on the X chromosome (Xq26.3) and encodes CD40 ligand (CD40L, also known as CD154), a type II transmembrane protein mainly expressed on activated T cells, platelets, and some B cells. Under inflammatory conditions, monocytes, natural killer cells, mast cells, and basophils can also be induced to express CD40L [2-4].
The interaction of CD40 with its ligand, CD40L (CD154), is a critical costimulatory signal essential for T-dependent humoral and cell-mediated immunity. This interaction triggers downstream signaling pathways, including NF-κB, JNK, and JAK/STAT, leading to B cell activation, proliferation, differentiation, isotype switching, memory B cell development, germinal center formation, and enhanced APC function and cytokine production [5]. Dysregulation of CD40/CD40L signaling pathway is implicated in the pathogenesis of numerous diseases, including autoimmune disorders like inflammatory bowel disease (IBD), type 1 diabetes (T1D), multiple sclerosis, and rheumatoid arthritis (RA), as well as cardiovascular diseases such as atherosclerosis, certain neurological conditions including Alzheimer's disease (AD) and traumatic brain injury, and various cancers [5-7].
Due to the important role of the CD40/CD40L interaction in immune activation, CD40/CD40L has been an important target for immunotherapy. In recent years, significant progress has been made in CD40/CD40L-targeted therapy. Various drugs have been developed, including agonistic/antagonistic monoclonal antibodies, cellular vaccines, adenoviral vectors, and protein antagonists, and have shown therapeutic potential in malignant tumors, autoimmune diseases, and allograft rejection [1].
The B6-hCD40/hCD40LG mouse is a dual-gene humanized model (for CD40 and CD40LG) generated by crossing B6-hCD40 mice (Catalog No.: C001721) with B6-hCD40LG mice (Catalog No.: C001720). The B6-hCD40/hCD40LG mouse model can be used for research on the mechanisms and therapeutic approaches of diseases such as autoimmune diseases, cancer, and cardiovascular diseases, as well as for the development of CD40/CD40L-targeted drugs.
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