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B6-hXDH
Product ID:
C001586
Strain:
C57BL/6NCya
Status:
Description:
Hyperuricemia is a metabolic disorder characterized by abnormally elevated levels of uric acid (UA) in the blood. Uric acid, the end product of purine metabolism, may crystallize as urate in joints, leading to gouty arthritis or form stones in the kidneys when its concentration is excessively high. The clinical manifestations of gout include hyperuricemia, recurrent acute gouty arthritis, deposition of tophi, chronic tophaceous arthritis, and joint deformities. It commonly affects the kidneys, causing chronic interstitial nephritis and uric acid nephrolithiasis [1-3]. By 2020, the global prevalence of hyperuricemia and gout surpassed 1.1 billion cases. In China, the number of patients is projected to reach 200 million for hyperuricemia and 43.25 million for gout by 2024 [2-3]. With the increasing disease burden, the demand for pharmacological interventions for hyperuricemia and gout continues to grow.
Hyperuricemia is closely related to uric acid levels in the body, and current therapeutic agents mainly target the reduction of uric acid synthesis or the promotion of uric acid excretion to manage the condition. Xanthine oxidoreductase (XOR) plays a critical role in purine metabolism by catalyzing the oxidation of hypoxanthine to xanthine and subsequently to uric acid. It is thus a key regulatory point in uric acid synthesis and an important target for hyperuricemia treatment [4-5]. XOR exists in two forms: the reduced xanthine dehydrogenase (XDH) and the oxidized xanthine oxidase (XO). XDH, in its reduced state, catalyzes the conversion of hypoxanthine to xanthine and uric acid, generating reduced nicotinamide adenine dinucleotide (NADH). In contrast, XO, in its oxidized state, converts xanthine to uric acid and hydrogen peroxide. The inhibition of XO by xanthine oxidase inhibitors (XOIs) to reduce uric acid production is a widely adopted therapeutic strategy for hyperuricemia and gout [6]. However, safety concerns remain with existing XOIs, highlighting the urgent need for novel therapeutics with improved safety profiles. Small interfering RNA (siRNA) represents a promising research focus in this area.
This strain is a humanized mouse model of the Xdh gene, generated by replacing the mouse Xdh gene with the complete human XDH gene sequence, including its untranslated regions (UTRs), exons, and introns. The B6-hXDH mice express the human XDH gene and xanthine oxidase protein in a pattern similar to the endogenous Xdh gene in mice, making their genetic, protein expression, and biochemical features highly comparable to humans. This strain serves as an ideal preclinical platform for studying the pathological mechanisms of hyperuricemia and gout and for developing novel xanthine oxidase inhibitors and nucleic acid therapies.
Hyperuricemia is a metabolic disorder characterized by abnormally elevated levels of uric acid (UA) in the blood. Uric acid, the end product of purine metabolism, may crystallize as urate in joints, leading to gouty arthritis or form stones in the kidneys when its concentration is excessively high. The clinical manifestations of gout include hyperuricemia, recurrent acute gouty arthritis, deposition of tophi, chronic tophaceous arthritis, and joint deformities. It commonly affects the kidneys, causing chronic interstitial nephritis and uric acid nephrolithiasis [1-3]. By 2020, the global prevalence of hyperuricemia and gout surpassed 1.1 billion cases. In China, the number of patients is projected to reach 200 million for hyperuricemia and 43.25 million for gout by 2024 [2-3]. With the increasing disease burden, the demand for pharmacological interventions for hyperuricemia and gout continues to grow.
Hyperuricemia is closely related to uric acid levels in the body, and current therapeutic agents mainly target the reduction of uric acid synthesis or the promotion of uric acid excretion to manage the condition. Xanthine oxidoreductase (XOR) plays a critical role in purine metabolism by catalyzing the oxidation of hypoxanthine to xanthine and subsequently to uric acid. It is thus a key regulatory point in uric acid synthesis and an important target for hyperuricemia treatment [4-5]. XOR exists in two forms: the reduced xanthine dehydrogenase (XDH) and the oxidized xanthine oxidase (XO). XDH, in its reduced state, catalyzes the conversion of hypoxanthine to xanthine and uric acid, generating reduced nicotinamide adenine dinucleotide (NADH). In contrast, XO, in its oxidized state, converts xanthine to uric acid and hydrogen peroxide. The inhibition of XO by xanthine oxidase inhibitors (XOIs) to reduce uric acid production is a widely adopted therapeutic strategy for hyperuricemia and gout [6]. However, safety concerns remain with existing XOIs, highlighting the urgent need for novel therapeutics with improved safety profiles. Small interfering RNA (siRNA) represents a promising research focus in this area.
This strain is a humanized mouse model of the Xdh gene, generated by replacing the mouse Xdh gene with the complete human XDH gene sequence, including its untranslated regions (UTRs), exons, and introns. The B6-hXDH mice express the human XDH gene and xanthine oxidase protein in a pattern similar to the endogenous Xdh gene in mice, making their genetic, protein expression, and biochemical features highly comparable to humans. This strain serves as an ideal preclinical platform for studying the pathological mechanisms of hyperuricemia and gout and for developing novel xanthine oxidase inhibitors and nucleic acid therapies.
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-huSLC16A1
Product ID:
C001915
Strain:
C57BL/6NCya
Status:
Description:
The SLC16A1 gene encodes the Monocarboxylate Transporter 1 (MCT1) protein, a vital proton-coupled symporter that facilitates the rapid transmembrane movement of metabolic substrates, including lactate, pyruvate, and ketone bodies (acetoacetate and β-hydroxybutyrate). This gene is ubiquitously expressed across nearly all human tissues to maintain energy balance and pH homeostasis, with notably high levels labeled in the heart, oxidative skeletal muscle fibers, erythrocytes (red blood cells), and the brain (specifically in oligodendrocytes and the blood-brain barrier), while being uniquely "disallowed" or suppressed in normal pancreatic beta-cells to prevent inappropriate insulin release [1]. Functionally, MCT1 is central to the "lactate shuttle" mechanism, allowing tissues to coordinate metabolic fuel exchange by facilitating either the influx or efflux of substrates depending on the concentration gradient and proton motive force [2]. Mutations in SLC16A1 are clinically linked to Erythrocyte Lactate Transporter Defect, which causes exercise-induced muscle cramping and fatigue, and Monocarboxylate Transporter 1 Deficiency, a rare disorder characterized by recurrent episodes of severe ketoacidosis and vomiting triggered by fasting or infection [3]. Conversely, gain-of-function mutations in the gene's promoter lead to familial hyperinsulinemia type 7 (HHF7), where exercise triggers excessive insulin secretion, while its widespread overexpression in various cancers (such as melanoma and lung cancer) supports the Warburg effect by managing lactate efflux to prevent intracellular acidification and fueling tumor progression [4].
The B6-huSLC16A1 mouse is a humanized model constructed through gene-editing technology, in which the sequences from the ATG start codon to the TGA stop codon of the endogenous mouse Slc16a1 gene are replaced with the sequences from the ATG start codon to the TGA stop codon of the human SLC16A1 gene. This model can be used for research on diseases such as Erythrocyte Lactate Transporter Defect, Monocarboxylate Transporter 1 Deficiency, familial hyperinsulinemia type 7 (HHF7), and various cancers, as well as for screening, development, and preclinical evaluation of SLC16A1-targeted therapeutics.
The SLC16A1 gene encodes the Monocarboxylate Transporter 1 (MCT1) protein, a vital proton-coupled symporter that facilitates the rapid transmembrane movement of metabolic substrates, including lactate, pyruvate, and ketone bodies (acetoacetate and β-hydroxybutyrate). This gene is ubiquitously expressed across nearly all human tissues to maintain energy balance and pH homeostasis, with notably high levels labeled in the heart, oxidative skeletal muscle fibers, erythrocytes (red blood cells), and the brain (specifically in oligodendrocytes and the blood-brain barrier), while being uniquely "disallowed" or suppressed in normal pancreatic beta-cells to prevent inappropriate insulin release [1]. Functionally, MCT1 is central to the "lactate shuttle" mechanism, allowing tissues to coordinate metabolic fuel exchange by facilitating either the influx or efflux of substrates depending on the concentration gradient and proton motive force [2]. Mutations in SLC16A1 are clinically linked to Erythrocyte Lactate Transporter Defect, which causes exercise-induced muscle cramping and fatigue, and Monocarboxylate Transporter 1 Deficiency, a rare disorder characterized by recurrent episodes of severe ketoacidosis and vomiting triggered by fasting or infection [3]. Conversely, gain-of-function mutations in the gene's promoter lead to familial hyperinsulinemia type 7 (HHF7), where exercise triggers excessive insulin secretion, while its widespread overexpression in various cancers (such as melanoma and lung cancer) supports the Warburg effect by managing lactate efflux to prevent intracellular acidification and fueling tumor progression [4].
The B6-huSLC16A1 mouse is a humanized model constructed through gene-editing technology, in which the sequences from the ATG start codon to the TGA stop codon of the endogenous mouse Slc16a1 gene are replaced with the sequences from the ATG start codon to the TGA stop codon of the human SLC16A1 gene. This model can be used for research on diseases such as Erythrocyte Lactate Transporter Defect, Monocarboxylate Transporter 1 Deficiency, familial hyperinsulinemia type 7 (HHF7), and various cancers, as well as for screening, development, and preclinical evaluation of SLC16A1-targeted therapeutics.
B6-Uox KO/huURAT1
Product ID:
C001937
Strain:
C57BL/6Cya
Status:
Description:
B6-Uox KO/huURAT1 mice are humanized disease models obtained by crossing Uox KO mice (catalog No.: C001232) with B6-huURAT1 mice (catalog No.: C001704). This model can be used for studying the pathological mechanisms and treatment methods of uric acid metabolism-related diseases such as hyperuricemia and gout, as well as for screening and developing URAT1-targeted therapies and evaluating preclinical efficacy and safety. It is worth noting that heterozygous Uox KO mice can survive and are fertile, while homozygous Uox KO mice need to be maintained with drugs such as Allopurinol after birth.
B6-Uox KO/huURAT1 mice are humanized disease models obtained by crossing Uox KO mice (catalog No.: C001232) with B6-huURAT1 mice (catalog No.: C001704). This model can be used for studying the pathological mechanisms and treatment methods of uric acid metabolism-related diseases such as hyperuricemia and gout, as well as for screening and developing URAT1-targeted therapies and evaluating preclinical efficacy and safety. It is worth noting that heterozygous Uox KO mice can survive and are fertile, while homozygous Uox KO mice need to be maintained with drugs such as Allopurinol after birth.
B6-Uox KO/huXDH
Product ID:
C001938
Strain:
C57BL/6Cya
Status:
Description:
The B6-Uox KO/huXDH mice are humanized disease models obtained by mating Uox KO mice (catalog No.: C001232) with B6-huXDH mice (catalog No.: C001586). This model is suitable for studying the pathological mechanisms of hyperuricemia and gout, and provides an ideal preclinical research platform for the development of novel xanthine oxidase inhibitors and small nucleic acid therapies. It is worth noting that heterozygous Uox KO mice can survive and are fertile, while homozygous Uox KO mice require drugs such as Allopurinol to maintain their survival after birth.
The B6-Uox KO/huXDH mice are humanized disease models obtained by mating Uox KO mice (catalog No.: C001232) with B6-huXDH mice (catalog No.: C001586). This model is suitable for studying the pathological mechanisms of hyperuricemia and gout, and provides an ideal preclinical research platform for the development of novel xanthine oxidase inhibitors and small nucleic acid therapies. It is worth noting that heterozygous Uox KO mice can survive and are fertile, while homozygous Uox KO mice require drugs such as Allopurinol to maintain their survival after birth.
hGLP1R(SD)
Product ID:
CR014
Strain:
SD
Status:
Description:
The glucagon-like peptide-1 receptor (GLP-1R), encoded by the GLP1R gene, is the receptor for endogenous glucagon-like peptide-1 (GLP-1) and belongs to the class B (secretin-like) G protein-coupled receptor (GPCR) family. GLP-1R contains a characteristic seven-transmembrane domain (7TM) and a relatively large N-terminal extracellular domain, and mediates downstream signaling upon binding to GLP-1 [1]. GLP-1R is predominantly expressed in pancreatic β cells and is also detected in the central nervous system and other tissues. Upon ligand activation, GLP-1R can undergo internalization and participate in the regulation of insulin secretion and energy metabolism [2-3]. Activation of GLP-1R enhances glucose-dependent insulin secretion and inhibits glucagon secretion, while also delaying gastric emptying and reducing food intake [3-4]. GLP-1 receptor agonists (GLP-1RAs) are important therapeutic agents for the treatment of type 2 diabetes (T2D) and obesity, and improve glycemic control and promote weight loss through these multiple mechanisms [4]. In addition, GLP-1R-related signaling has been extensively investigated for its potential neuroprotective effects. Neuroprotective effects of GLP-1R agonists have been observed in animal models of stroke, although their clinical value for the direct treatment of acute stroke requires further investigation [5].
The hGLP1R(SD) Rat was generated by gene editing to replace a partial coding sequence of exon 1 and a partial sequence of intron 1 of the rat Glp1r gene with "Exon 1~2 of Human GLP1R CDS (without signal peptide)-Human GLP1R intron 2-Exon 3~13 of Human GLP1R CDS-hGH pA", while retaining the genomic sequence encoding the signal peptide of rat GLP1R. Its potential applications mainly include mechanistic studies of type 2 diabetes (T2D), obesity, and other metabolic diseases, as well as pharmacological studies of GLP-1R-targeted therapeutics, candidate drug screening, and evaluation of their potential effects.
The glucagon-like peptide-1 receptor (GLP-1R), encoded by the GLP1R gene, is the receptor for endogenous glucagon-like peptide-1 (GLP-1) and belongs to the class B (secretin-like) G protein-coupled receptor (GPCR) family. GLP-1R contains a characteristic seven-transmembrane domain (7TM) and a relatively large N-terminal extracellular domain, and mediates downstream signaling upon binding to GLP-1 [1]. GLP-1R is predominantly expressed in pancreatic β cells and is also detected in the central nervous system and other tissues. Upon ligand activation, GLP-1R can undergo internalization and participate in the regulation of insulin secretion and energy metabolism [2-3]. Activation of GLP-1R enhances glucose-dependent insulin secretion and inhibits glucagon secretion, while also delaying gastric emptying and reducing food intake [3-4]. GLP-1 receptor agonists (GLP-1RAs) are important therapeutic agents for the treatment of type 2 diabetes (T2D) and obesity, and improve glycemic control and promote weight loss through these multiple mechanisms [4]. In addition, GLP-1R-related signaling has been extensively investigated for its potential neuroprotective effects. Neuroprotective effects of GLP-1R agonists have been observed in animal models of stroke, although their clinical value for the direct treatment of acute stroke requires further investigation [5].
The hGLP1R(SD) Rat was generated by gene editing to replace a partial coding sequence of exon 1 and a partial sequence of intron 1 of the rat Glp1r gene with "Exon 1~2 of Human GLP1R CDS (without signal peptide)-Human GLP1R intron 2-Exon 3~13 of Human GLP1R CDS-hGH pA", while retaining the genomic sequence encoding the signal peptide of rat GLP1R. Its potential applications mainly include mechanistic studies of type 2 diabetes (T2D), obesity, and other metabolic diseases, as well as pharmacological studies of GLP-1R-targeted therapeutics, candidate drug screening, and evaluation of their potential effects.
hGLP1R/hGIPR/huGCGR
Product ID:
C001939
Strain:
C57BL/6NCya
Status:
Description:
The hGLP1R/hGIPR/huGCGR mouse is a triple-gene humanized model obtained by mating hGLP1R/hGIPR mice (catalog No.: C001599) with huGCGR mice (catalog No.: C001723). This model can be used for studying the pathogenic mechanisms and developing treatment methods for glucose-related metabolic diseases such as obesity, type 2 diabetes (T2D), and steatohepatitis, as well as for the development of GIPR/GLP-1R/GCGR-targeted drugs.
The hGLP1R/hGIPR/huGCGR mouse is a triple-gene humanized model obtained by mating hGLP1R/hGIPR mice (catalog No.: C001599) with huGCGR mice (catalog No.: C001723). This model can be used for studying the pathogenic mechanisms and developing treatment methods for glucose-related metabolic diseases such as obesity, type 2 diabetes (T2D), and steatohepatitis, as well as for the development of GIPR/GLP-1R/GCGR-targeted drugs.
huGCGR/hGLP1R
Product ID:
C001785
Strain:
C57BL/6NCya
Status:
Description:
The huGCGR/hGLP1R mouse is a dual-gene humanized model obtained by mating huGCGR mice (catalog No.: C001723) with hGLP1R mice (catalog No.: C001421). This model can be used for studying the pathogenesis of glucose-related metabolic diseases such as obesity, type 2 diabetes (T2D), and steatohepatitis, as well as for the screening, development, and safety evaluation of drugs targeting GCGR/GLP1R.
The huGCGR/hGLP1R mouse is a dual-gene humanized model obtained by mating huGCGR mice (catalog No.: C001723) with hGLP1R mice (catalog No.: C001421). This model can be used for studying the pathogenesis of glucose-related metabolic diseases such as obesity, type 2 diabetes (T2D), and steatohepatitis, as well as for the screening, development, and safety evaluation of drugs targeting GCGR/GLP1R.
hutau/hGLP1R
Product ID:
I001221
Strain:
C57BL/6Cya
Status:
Description:
The tau protein, a microtubule-associated protein encoded by MAPT is primarily localized to neuronal axons and plays a critical role in microtubule stability and assembly. By binding to microtubules, tau protein helps to maintain neuronal cell shape. Mutations in MAPT can promote tau aggregation, leading to pathological tau protein accumulation and death of glutamatergic cortical neurons [1]. Additionally, certain MAPT mutations can affect pre-mRNA exon splicing, altering the ratio of 3R to 4R tau protein isoforms and increasing the relative production of 4R-tau protein, which is more prone to fibril formation [2].
The GLP-1 receptor (GLP-1R) gene encodes a protein that serves as the receptor for the glucagon-like peptide 1 (GLP-1) hormone, belonging to the glucagon receptor subfamily within the class B G-protein-coupled receptors (GPCRs). G proteins are a class of intracellular signal transduction proteins typically associated with seven-transmembrane receptors (GPCRs). When a GPCR binds to its ligand, it activates the G protein, causing it to dissociate from the Gβγ subunit and initiate downstream effects through interactions with membrane-bound effector molecules. This signaling process is known as canonical G protein signaling. GLP-1R is a multi-transmembrane protein characterized by a typical seven-transmembrane core domain and a relatively large extracellular domain, which can stimulate glucose-induced insulin secretion [3]. GLP-1R is a cell surface receptor protein widely expressed in tissues such as the brain, small intestine, heart, and lungs. It internalizes in response to GLP-1 and GLP-1 analogs and plays a crucial role in the insulin secretion signaling cascade. Additionally, data from animal models indicate its neuroprotective effects [4-5]. Polymorphisms of this gene are closely associated with diabetes. The GLP1R protein is an important drug target for treating type 2 diabetes and stroke. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new class of antidiabetic drugs in recent years. They activate GLP1R to enhance insulin secretion, suppress glucagon secretion, delay gastric emptying, and reduce food intake through central appetite suppression, lowering blood glucose and weight loss [6].
The hutau/hGLP1R mouse is obtained by mating hutau(MAPT) mice (Catalog No.: C001410) with hGLP1R mice (Catalog No.: C001421). This model can be used for research on neurodegenerative diseases such as frontotemporal dementia (FTD) and Alzheimer's disease (AD), as well as metabolic diseases such as obesity and type 2 diabetes. It is also useful for developing GLP-1 receptor agonist (GLP-1RA) drugs or for the preclinical evaluation of the potential therapeutic effects of GLP-1RA drugs in tauopathy-related diseases like Alzheimer's disease (AD).
The tau protein, a microtubule-associated protein encoded by MAPT is primarily localized to neuronal axons and plays a critical role in microtubule stability and assembly. By binding to microtubules, tau protein helps to maintain neuronal cell shape. Mutations in MAPT can promote tau aggregation, leading to pathological tau protein accumulation and death of glutamatergic cortical neurons [1]. Additionally, certain MAPT mutations can affect pre-mRNA exon splicing, altering the ratio of 3R to 4R tau protein isoforms and increasing the relative production of 4R-tau protein, which is more prone to fibril formation [2].
The GLP-1 receptor (GLP-1R) gene encodes a protein that serves as the receptor for the glucagon-like peptide 1 (GLP-1) hormone, belonging to the glucagon receptor subfamily within the class B G-protein-coupled receptors (GPCRs). G proteins are a class of intracellular signal transduction proteins typically associated with seven-transmembrane receptors (GPCRs). When a GPCR binds to its ligand, it activates the G protein, causing it to dissociate from the Gβγ subunit and initiate downstream effects through interactions with membrane-bound effector molecules. This signaling process is known as canonical G protein signaling. GLP-1R is a multi-transmembrane protein characterized by a typical seven-transmembrane core domain and a relatively large extracellular domain, which can stimulate glucose-induced insulin secretion [3]. GLP-1R is a cell surface receptor protein widely expressed in tissues such as the brain, small intestine, heart, and lungs. It internalizes in response to GLP-1 and GLP-1 analogs and plays a crucial role in the insulin secretion signaling cascade. Additionally, data from animal models indicate its neuroprotective effects [4-5]. Polymorphisms of this gene are closely associated with diabetes. The GLP1R protein is an important drug target for treating type 2 diabetes and stroke. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new class of antidiabetic drugs in recent years. They activate GLP1R to enhance insulin secretion, suppress glucagon secretion, delay gastric emptying, and reduce food intake through central appetite suppression, lowering blood glucose and weight loss [6].
The hutau/hGLP1R mouse is obtained by mating hutau(MAPT) mice (Catalog No.: C001410) with hGLP1R mice (Catalog No.: C001421). This model can be used for research on neurodegenerative diseases such as frontotemporal dementia (FTD) and Alzheimer's disease (AD), as well as metabolic diseases such as obesity and type 2 diabetes. It is also useful for developing GLP-1 receptor agonist (GLP-1RA) drugs or for the preclinical evaluation of the potential therapeutic effects of GLP-1RA drugs in tauopathy-related diseases like Alzheimer's disease (AD).
hGLP1R/Lep-KO(ob/ob)
Product ID:
C001601
Strain:
C57BL/6NCya;C57BL/6JCya
Status:
Description:
The Glucagon-like peptide 1 receptor (GLP1R) gene encodes a protein that belongs to the glucagon receptor subfamily of the G protein-coupled receptor B cluster [1]. This cell surface receptor protein is widely expressed in tissues such as the brain, small intestine, heart, and lungs, and plays a crucial role in insulin secretion signaling cascades by responding to GLP-1 and GLP-1 analogs. Animal model data also suggest that it has neuroprotective effects. Polymorphisms of this gene are closely associated with diabetes, making the GLP-1R protein an important drug target for the treatment of type 2 diabetes and stroke [2-3]. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are novel anti-diabetic drugs that activate GLP-1R to enhance insulin secretion, inhibit glucagon secretion, delay gastric emptying, and reduce food intake through central appetite suppression, thereby achieving blood sugar reduction and weight loss [4].
The leptin (LEP) gene, also known as the OB gene, encodes the leptin protein, which is secreted into the circulation by white adipocytes and plays a major role in regulating energy homeostasis. Circulating leptin binds to leptin receptors (LEPR) in the brain, activating downstream signaling pathways that inhibit feeding and promote energy expenditure. Leptin also has multiple endocrine functions and is involved in physiopathological processes such as immune and inflammatory responses, hematopoiesis, angiogenesis, reproduction, bone formation, and wound healing [6]. Mutations in the LEP gene and its regulatory regions lead to severe obesity and morbid obesity with hypogonadism in humans and are also associated with the development of type II diabetes [7].
The hGLP1R/Lep-KO(ob/ob) mouse model, generated by mating hGLP1R mice (Catalog Number: C001421) with Lep-KO (ob/ob) mice (Catalog Number: C001368), is a metabolic disease model. It can be used for research on the pathogenic mechanisms of various metabolic diseases, such as obesity and type II diabetes, and for screening GLP-1RA drugs.
The Glucagon-like peptide 1 receptor (GLP1R) gene encodes a protein that belongs to the glucagon receptor subfamily of the G protein-coupled receptor B cluster [1]. This cell surface receptor protein is widely expressed in tissues such as the brain, small intestine, heart, and lungs, and plays a crucial role in insulin secretion signaling cascades by responding to GLP-1 and GLP-1 analogs. Animal model data also suggest that it has neuroprotective effects. Polymorphisms of this gene are closely associated with diabetes, making the GLP-1R protein an important drug target for the treatment of type 2 diabetes and stroke [2-3]. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are novel anti-diabetic drugs that activate GLP-1R to enhance insulin secretion, inhibit glucagon secretion, delay gastric emptying, and reduce food intake through central appetite suppression, thereby achieving blood sugar reduction and weight loss [4].
The leptin (LEP) gene, also known as the OB gene, encodes the leptin protein, which is secreted into the circulation by white adipocytes and plays a major role in regulating energy homeostasis. Circulating leptin binds to leptin receptors (LEPR) in the brain, activating downstream signaling pathways that inhibit feeding and promote energy expenditure. Leptin also has multiple endocrine functions and is involved in physiopathological processes such as immune and inflammatory responses, hematopoiesis, angiogenesis, reproduction, bone formation, and wound healing [6]. Mutations in the LEP gene and its regulatory regions lead to severe obesity and morbid obesity with hypogonadism in humans and are also associated with the development of type II diabetes [7].
The hGLP1R/Lep-KO(ob/ob) mouse model, generated by mating hGLP1R mice (Catalog Number: C001421) with Lep-KO (ob/ob) mice (Catalog Number: C001368), is a metabolic disease model. It can be used for research on the pathogenic mechanisms of various metabolic diseases, such as obesity and type II diabetes, and for screening GLP-1RA drugs.
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