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Apoe-KO(6J)
Product ID:
C001507
Strain:
C57BL/6JCya
Status:
Description:
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 [1]. 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 [2]. 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 [1-4]. In addition, ApoE forms a complex with activated C1q, becoming a checkpoint inhibitor target of the classical complement pathway [5]. 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 Apoe-KO(6J) mouse is a model of ApoE deficiency. It was generated by gene editing technology to knock out the Apoe gene in mice. ApoE protein synthesis is blocked in these mice, leading to elevated cholesterol levels and spontaneous atherosclerosis. Cholesterol levels and atherosclerosis in mice fed a high-fat diet (HFD) are further exacerbated. The Apoe-KO(6J) mice are viable and can be used for research in hypercholesterolemia, atherosclerosis, and Alzheimer's disease.
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 [1]. 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 [2]. 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 [1-4]. In addition, ApoE forms a complex with activated C1q, becoming a checkpoint inhibitor target of the classical complement pathway [5]. 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 Apoe-KO(6J) mouse is a model of ApoE deficiency. It was generated by gene editing technology to knock out the Apoe gene in mice. ApoE protein synthesis is blocked in these mice, leading to elevated cholesterol levels and spontaneous atherosclerosis. Cholesterol levels and atherosclerosis in mice fed a high-fat diet (HFD) are further exacerbated. The Apoe-KO(6J) mice are viable and can be used for research in hypercholesterolemia, atherosclerosis, and Alzheimer's disease.
huAPOE2
Product ID:
C002043
Strain:
C57BL/6JCya
Status:
Description:
Apolipoprotein E ε2 (APOE2) is one of the three major human APOE isoforms, characterized by the amino acid signature Cys112/Cys158. The APOE gene is primarily expressed in the liver and central nervous system, where it is synthesized by hepatocytes and astrocytes to encode a 299-amino acid glycoprotein [1]. As a key ligand for the low-density lipoprotein (LDL) receptor family, APOE plays a critical role in cholesterol and triglyceride transport, lipoprotein metabolism, neuronal membrane repair, and the maintenance of synaptic plasticity [1-2]. Compared to APOE3, APOE2 exhibits significantly reduced binding affinity for LDL receptors, which impairs lipid clearance efficiency. Under specific genetic backgrounds, the APOE2 homozygous state can lead to Familial Dysbetalipoproteinemia (Type III Hyperlipoproteinemia) [2]. Furthermore, in contrast to APOE4, APOE2 is generally considered to possess neuroprotective properties and is associated with a reduced risk of Alzheimer's disease (AD) [3].
The huAPOE2 mouse is a humanized model generated via gene editing. The exons 2-4 plus partial flanking sequences of the mouse Apoe gene were replaced with the human APOE gene sequence including exons 2-4 and some downstream sequence of 3'UTR. The point mutation p.R176C (CGC to TGC) was introduced into the human APOE exon 4. This model is suitable for studying dyslipidemia, atherosclerosis, Type III hyperlipoproteinemia, neuroinflammation, Alzheimer's disease (AD), and other APOE2-associated disorders.
Apolipoprotein E ε2 (APOE2) is one of the three major human APOE isoforms, characterized by the amino acid signature Cys112/Cys158. The APOE gene is primarily expressed in the liver and central nervous system, where it is synthesized by hepatocytes and astrocytes to encode a 299-amino acid glycoprotein [1]. As a key ligand for the low-density lipoprotein (LDL) receptor family, APOE plays a critical role in cholesterol and triglyceride transport, lipoprotein metabolism, neuronal membrane repair, and the maintenance of synaptic plasticity [1-2]. Compared to APOE3, APOE2 exhibits significantly reduced binding affinity for LDL receptors, which impairs lipid clearance efficiency. Under specific genetic backgrounds, the APOE2 homozygous state can lead to Familial Dysbetalipoproteinemia (Type III Hyperlipoproteinemia) [2]. Furthermore, in contrast to APOE4, APOE2 is generally considered to possess neuroprotective properties and is associated with a reduced risk of Alzheimer's disease (AD) [3].
The huAPOE2 mouse is a humanized model generated via gene editing. The exons 2-4 plus partial flanking sequences of the mouse Apoe gene were replaced with the human APOE gene sequence including exons 2-4 and some downstream sequence of 3'UTR. The point mutation p.R176C (CGC to TGC) was introduced into the human APOE exon 4. This model is suitable for studying dyslipidemia, atherosclerosis, Type III hyperlipoproteinemia, neuroinflammation, Alzheimer's disease (AD), and other APOE2-associated disorders.
huAPOE3
Product ID:
C002021
Strain:
C57BL/6JCya
Status:
Description:
The APOE3 (Apolipoprotein E epsilon 3) gene represents the most prevalent isoform within the human population and is typically categorized as the functionally "neutral" or wild-type allele. Predominantly expressed in the liver and central nervous system, it is produced by hepatocytes and astrocytes to encode the 299-amino acid Apolipoprotein E glycoprotein [1]. This protein serves as a vital ligand for LDL receptors, facilitating the systemic transport and redistribution of cholesterol and triglycerides necessary for membrane stability and neural synaptic repair. While APOE3 generally supports healthy lipid homeostasis, the APOE4 isoform is associated with increased risk of cardiovascular pathologies like atherosclerosis, whereas APOE2 homozygosity (or rare APOE variants) can lead to familial dysbetalipoproteinemia in specific genetic contexts [2]. Furthermore, it serves as the baseline for assessing neurodegenerative risk, sitting between the neuroprotective effects of the APOE2 variant and the significantly increased Alzheimer's disease risk associated with APOE4 [3].
The huAPOE3 mouse is a humanized model constructed by using gene-editing technology to replace exons 2-4 and part of the flanking sequences of the mouse Apoe gene with the human APOE gene sequences, including exons 2, 3, 4, and some downstream sequence of 3’UTR. This model can be used for research on cardiovascular diseases, such as atherosclerosis, and neurodegenerative diseases, such as Alzheimer's disease (AD), as well as for the development of APOE3-targeted drugs.
The APOE3 (Apolipoprotein E epsilon 3) gene represents the most prevalent isoform within the human population and is typically categorized as the functionally "neutral" or wild-type allele. Predominantly expressed in the liver and central nervous system, it is produced by hepatocytes and astrocytes to encode the 299-amino acid Apolipoprotein E glycoprotein [1]. This protein serves as a vital ligand for LDL receptors, facilitating the systemic transport and redistribution of cholesterol and triglycerides necessary for membrane stability and neural synaptic repair. While APOE3 generally supports healthy lipid homeostasis, the APOE4 isoform is associated with increased risk of cardiovascular pathologies like atherosclerosis, whereas APOE2 homozygosity (or rare APOE variants) can lead to familial dysbetalipoproteinemia in specific genetic contexts [2]. Furthermore, it serves as the baseline for assessing neurodegenerative risk, sitting between the neuroprotective effects of the APOE2 variant and the significantly increased Alzheimer's disease risk associated with APOE4 [3].
The huAPOE3 mouse is a humanized model constructed by using gene-editing technology to replace exons 2-4 and part of the flanking sequences of the mouse Apoe gene with the human APOE gene sequences, including exons 2, 3, 4, and some downstream sequence of 3’UTR. This model can be used for research on cardiovascular diseases, such as atherosclerosis, and neurodegenerative diseases, such as Alzheimer's disease (AD), as well as for the development of APOE3-targeted drugs.
huAPOE4
Product ID:
C001867
Strain:
C57BL/6JCya
Status:
Description:
Apolipoprotein E (APOE) is a critical apolipoprotein involved in lipid transport mediated by lipoproteins. As a core component of plasma lipoproteins, APOE facilitates the transport of lipids through plasma and interstitial fluid between organs, and it plays a pivotal role in the generation, conversion, and clearance of lipoproteins. In humans, the APOE gene has three isoforms (E2, E3, E4) associated with atherosclerosis and Alzheimer’s disease (AD), with the E4 allele present in approximately 14% of the population [1]. The ApoE4 isoform is a major genetic risk factor for late-onset Alzheimer’s disease (AD), exacerbating neurodegeneration. ApoE4-associated damage to vascular systems in the brain could have a key role in AD pathogenesis [2]. Beyond AD, APOE4 is linked to cardiovascular diseases due to its influence on lipid homeostasis [3].
huAPOE4 mice are humanized models constructed through gene editing technology. Exons 2-4 plus partial flanking sequences of the mouse Apoe gene were replaced in situ with the Mutant human APOE gene sequence, including exons 2, 3, and 4 and some downstream sequence of 3’UTR. The p.C130R (TGC to CGC) was introduced into the mutant human APOE gene. This model can be used for research on the pathogenic mechanisms and treatment methods of cardiovascular diseases such as diet-induced hypercholesterolemia, atherosclerosis, and lipid metabolism. It can also be used to study the role of human APOE gene polymorphisms in Alzheimer's disease.
Apolipoprotein E (APOE) is a critical apolipoprotein involved in lipid transport mediated by lipoproteins. As a core component of plasma lipoproteins, APOE facilitates the transport of lipids through plasma and interstitial fluid between organs, and it plays a pivotal role in the generation, conversion, and clearance of lipoproteins. In humans, the APOE gene has three isoforms (E2, E3, E4) associated with atherosclerosis and Alzheimer’s disease (AD), with the E4 allele present in approximately 14% of the population [1]. The ApoE4 isoform is a major genetic risk factor for late-onset Alzheimer’s disease (AD), exacerbating neurodegeneration. ApoE4-associated damage to vascular systems in the brain could have a key role in AD pathogenesis [2]. Beyond AD, APOE4 is linked to cardiovascular diseases due to its influence on lipid homeostasis [3].
huAPOE4 mice are humanized models constructed through gene editing technology. Exons 2-4 plus partial flanking sequences of the mouse Apoe gene were replaced in situ with the Mutant human APOE gene sequence, including exons 2, 3, and 4 and some downstream sequence of 3’UTR. The p.C130R (TGC to CGC) was introduced into the mutant human APOE gene. This model can be used for research on the pathogenic mechanisms and treatment methods of cardiovascular diseases such as diet-induced hypercholesterolemia, atherosclerosis, and lipid metabolism. It can also be used to study the role of human APOE gene polymorphisms in Alzheimer's disease.
Apoe-KO
Product ID:
S-KO-22621
Strain:
C57BL/6JCya
Status:
Description:
Apoe is located on chromosome 7 of mice. Nuclease Technology was used to design sgRNA; Apoe knockout mice were obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.
Apoe is located on chromosome 7 of mice. Nuclease Technology was used to design sgRNA; Apoe knockout mice were obtained by applying high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.
Apoe-flox
Product ID:
S-CKO-01263
Strain:
C57BL/6JCya
Status:
Description:
Apoe is located on chromosome 7 of mice. SgRNA and ssDNA were designed using Nuclease Technology; Apoe conditional knockout mice were obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.
Apoe is located on chromosome 7 of mice. SgRNA and ssDNA were designed using Nuclease Technology; Apoe conditional knockout mice were obtained by high-throughput electroporation of fertilized eggs. After sexual maturity, sperm were collected for cryopreservation.
huPCSK9/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 huPCSK9/Apoe-KO mice are obtained by crossing huPCSK9 mice (Catalog No.: C001617) with Apoe-KO(6J) mice (Catalog No.: C001507). Apoe-KO(6J) 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, huPCSK9 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 huPCSK9/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 huPCSK9/Apoe-KO mice are obtained by crossing huPCSK9 mice (Catalog No.: C001617) with Apoe-KO(6J) mice (Catalog No.: C001507). Apoe-KO(6J) 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, huPCSK9 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 huPCSK9/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.
huAPOE4/huTFRC
Product ID:
C002106
Strain:
C57BL/6J;6NCya
Status:
Description:
Apolipoprotein E (APOE) is a critical apolipoprotein involved in lipoprotein-mediated lipid transport. As a core component of plasma lipoproteins, APOE facilitates the transport of lipids between organs through plasma and interstitial fluid and plays a pivotal role in the generation, conversion, and clearance of lipoproteins. In humans, the APOE gene has three major alleles (E2, E3, and E4), which are closely associated with atherosclerosis and Alzheimer’s disease (AD). The estimated global frequency of the E4 allele is approximately 14% [1]. The ApoE4 isoform is a major genetic risk factor for late-onset AD and exacerbates neurodegeneration. In addition, ApoE4-associated cerebrovascular damage may play a key role in the pathogenesis of AD [2]. Beyond AD, APOE4 also affects lipid homeostasis and is therefore associated with cardiovascular diseases [3].
The Transferrin receptor (TFRC) gene encodes Transferrin Receptor 1 (TFR1), a protein that is expressed at low levels in most normal cells but shows increased expression in highly proliferative cells, such as basal epidermal cells, intestinal epithelium, and certain activated immune cells. Brain capillary endothelial cells, which constitute the blood-brain barrier (BBB), also express this receptor at high levels [4]. TFR1 plays a critical role in maintaining iron metabolism and homeostasis by facilitating receptor-mediated endocytosis of iron-bound transferrin (Tf) via Tf cycling, thereby promoting iron uptake [5].
The huAPOE4/huTFRC mouse is a dual-gene humanized model obtained by crossing the huTFRC mouse (Catalog No.: C001860) with the huAPOE4 mouse (Catalog No.: C001867). This model can be utilized for the screening, pharmacodynamic evaluation, safety assessment, and mechanism of action studies of therapeutics targeting APOE4 and TFRC, as well as research on Alzheimer’s disease (AD) and blood-brain barrier (BBB) drug delivery, providing a preclinical research platform for developing related innovative therapies.
Apolipoprotein E (APOE) is a critical apolipoprotein involved in lipoprotein-mediated lipid transport. As a core component of plasma lipoproteins, APOE facilitates the transport of lipids between organs through plasma and interstitial fluid and plays a pivotal role in the generation, conversion, and clearance of lipoproteins. In humans, the APOE gene has three major alleles (E2, E3, and E4), which are closely associated with atherosclerosis and Alzheimer’s disease (AD). The estimated global frequency of the E4 allele is approximately 14% [1]. The ApoE4 isoform is a major genetic risk factor for late-onset AD and exacerbates neurodegeneration. In addition, ApoE4-associated cerebrovascular damage may play a key role in the pathogenesis of AD [2]. Beyond AD, APOE4 also affects lipid homeostasis and is therefore associated with cardiovascular diseases [3].
The Transferrin receptor (TFRC) gene encodes Transferrin Receptor 1 (TFR1), a protein that is expressed at low levels in most normal cells but shows increased expression in highly proliferative cells, such as basal epidermal cells, intestinal epithelium, and certain activated immune cells. Brain capillary endothelial cells, which constitute the blood-brain barrier (BBB), also express this receptor at high levels [4]. TFR1 plays a critical role in maintaining iron metabolism and homeostasis by facilitating receptor-mediated endocytosis of iron-bound transferrin (Tf) via Tf cycling, thereby promoting iron uptake [5].
The huAPOE4/huTFRC mouse is a dual-gene humanized model obtained by crossing the huTFRC mouse (Catalog No.: C001860) with the huAPOE4 mouse (Catalog No.: C001867). This model can be utilized for the screening, pharmacodynamic evaluation, safety assessment, and mechanism of action studies of therapeutics targeting APOE4 and TFRC, as well as research on Alzheimer’s disease (AD) and blood-brain barrier (BBB) drug delivery, providing a preclinical research platform for developing related innovative therapies.
pAPOE-huPNPLA3-I148M
Product ID:
C002109
Strain:
C57BL/6Cya
Status:
Description:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, characterized by excessive hepatic fat accumulation. Driven by metabolic risk factors, such as obesity, type 2 diabetes, and insulin resistance, MASLD can progressively advance to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC) [1-2]. PNPLA3-I148M (rs738409 C>G) is currently recognized as the strongest genetic susceptibility factor for MASLD. Individuals carrying this variant exhibit significantly increased hepatic fat content, with an approximately 2- to 3.5-fold increase in the risk of developing MASH, fibrosis, and cirrhosis, and this effect may act independently or synergistically with metabolic factors including obesity and insulin resistance [3-5]. Mechanistically, the PNPLA3-I148M mutant protein inhibits ATGL-mediated triglyceride (TG) hydrolysis by sequestering ABHD5, leading to hepatic lipid accumulation. Concurrently, this mutation triggers lipidomic remodeling characterized by enrichment of unsaturated fatty acids, elevated ceramides, and depletion of n-3 polyunsaturated fatty acids, and activates oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and inflammatory signaling pathways (e.g., STAT3), ultimately promoting hepatic stellate cell activation and fibrosis progression [6-7]. Studies have shown that the use of the human APOE promoter can drive specific high-level expression of PNPLA3-I148M in the liver, thereby recapitulating the human fatty liver phenotype associated with this variant in animal models [8].
The pAPOE-huPNPLA3-I148M mice are a disease model generated via gene editing, in which the murine Pnpla3 locus is replaced by a human PNPLA3 sequence driven by the human APOE promoter, with a p.I148M mutation (ATC to ATG) introduced into exon 3. This model is suitable for investigating the mechanisms of hepatic metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), as well as for drug screening, development, and preclinical in vivo evaluation targeting PNPLA3-I148M.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, characterized by excessive hepatic fat accumulation. Driven by metabolic risk factors, such as obesity, type 2 diabetes, and insulin resistance, MASLD can progressively advance to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC) [1-2]. PNPLA3-I148M (rs738409 C>G) is currently recognized as the strongest genetic susceptibility factor for MASLD. Individuals carrying this variant exhibit significantly increased hepatic fat content, with an approximately 2- to 3.5-fold increase in the risk of developing MASH, fibrosis, and cirrhosis, and this effect may act independently or synergistically with metabolic factors including obesity and insulin resistance [3-5]. Mechanistically, the PNPLA3-I148M mutant protein inhibits ATGL-mediated triglyceride (TG) hydrolysis by sequestering ABHD5, leading to hepatic lipid accumulation. Concurrently, this mutation triggers lipidomic remodeling characterized by enrichment of unsaturated fatty acids, elevated ceramides, and depletion of n-3 polyunsaturated fatty acids, and activates oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and inflammatory signaling pathways (e.g., STAT3), ultimately promoting hepatic stellate cell activation and fibrosis progression [6-7]. Studies have shown that the use of the human APOE promoter can drive specific high-level expression of PNPLA3-I148M in the liver, thereby recapitulating the human fatty liver phenotype associated with this variant in animal models [8].
The pAPOE-huPNPLA3-I148M mice are a disease model generated via gene editing, in which the murine Pnpla3 locus is replaced by a human PNPLA3 sequence driven by the human APOE promoter, with a p.I148M mutation (ATC to ATG) introduced into exon 3. This model is suitable for investigating the mechanisms of hepatic metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), as well as for drug screening, development, and preclinical in vivo evaluation targeting PNPLA3-I148M.
Ldlr KO (em)
Product ID:
C001392
Strain:
C57BL/6JCya
Status:
Description:
The Low-density lipoprotein receptor (LDLR) gene encodes a protein that is one of the hepatocyte surface receptors that binds apolipoprotein E (APOE) and thus removes lipoprotein particles from the blood. LDLR also plays an important role in cholesterol homeostasis by interacting with apolipoprotein B (APOB) on low-density lipoprotein (LDL) particles (the major cholesterol-carrying lipoprotein in plasma) to bind LDL and transport it into cells by endocytosis, thus maintaining plasma LDL levels [1-2]. This process occurs mainly in the liver, which removes approximately 70% of LDL from the circulation, and LDLR regulates plasma cholesterol levels by removing LDL and intermediate-density lipoproteins (IDL) from the plasma. Loss-of-function mutations in the LDLR gene cause familial hypercholesterolemia (FHCL1), a lipoprotein disorder characterized by elevated LDL cholesterol levels. The disease causes excessive deposition of cholesterol in tissues, which subsequently leads to macular tumors, accelerated atherosclerosis, and an increased risk of premature coronary heart disease [3-4].
This strain is an Ldlr deletion mouse model that uses gene editing technology to knock out the expression of human LDLR gene homolog in mice with impaired LDLR receptor synthesis, resulting in elevated serum cholesterol levels, which are further exacerbated by feeding on a high-fat diet (HFD), and the formation of aortic plaques. Homozygous Ldlr KO mice are viable and fertile and can be used for studies such as hypercholesterolemia and atherosclerosis. A similar strain includes Ldlr KO (tm) (catalog number: C001278), which was constructed using embryonic stem (ES) cell technology.
The Low-density lipoprotein receptor (LDLR) gene encodes a protein that is one of the hepatocyte surface receptors that binds apolipoprotein E (APOE) and thus removes lipoprotein particles from the blood. LDLR also plays an important role in cholesterol homeostasis by interacting with apolipoprotein B (APOB) on low-density lipoprotein (LDL) particles (the major cholesterol-carrying lipoprotein in plasma) to bind LDL and transport it into cells by endocytosis, thus maintaining plasma LDL levels [1-2]. This process occurs mainly in the liver, which removes approximately 70% of LDL from the circulation, and LDLR regulates plasma cholesterol levels by removing LDL and intermediate-density lipoproteins (IDL) from the plasma. Loss-of-function mutations in the LDLR gene cause familial hypercholesterolemia (FHCL1), a lipoprotein disorder characterized by elevated LDL cholesterol levels. The disease causes excessive deposition of cholesterol in tissues, which subsequently leads to macular tumors, accelerated atherosclerosis, and an increased risk of premature coronary heart disease [3-4].
This strain is an Ldlr deletion mouse model that uses gene editing technology to knock out the expression of human LDLR gene homolog in mice with impaired LDLR receptor synthesis, resulting in elevated serum cholesterol levels, which are further exacerbated by feeding on a high-fat diet (HFD), and the formation of aortic plaques. Homozygous Ldlr KO mice are viable and fertile and can be used for studies such as hypercholesterolemia and atherosclerosis. A similar strain includes Ldlr KO (tm) (catalog number: C001278), which was constructed using embryonic stem (ES) cell technology.
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