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huINHBE
製品ID :
C001533
系統:
C57BL/6NCya
状況:
説明:
Inhibin βE subunit (INHBE) is a member of the transforming growth factor-β (TGF-β) superfamily, highly specifically expressed in liver cells. The precursor protein of INHBE generates the inhibin β subunit after proteolytic processing. This protein is associated with various cellular processes, including cell proliferation, apoptosis, immune response, and hormone secretion. During the development of obesity and diabetes, the expression of INHBE protein inhibits the proliferation and growth of relevant cells in the pancreas and liver. Research has found a positive correlation between INHBE expression in the liver and insulin resistance and body mass index (BMI), suggesting that INHBE may be a liver factor in altering systemic metabolic status under conditions of obesity-related insulin resistance [1].
The studies conducted by Alnylam Pharmaceuticals and the Regeneron Genetics Center (RGC), respectively, revealed the close relationship between INHBE and fat regulation. The research demonstrated that rare loss-of-function variants in INHBE may protect the liver from the impact of inflammation, abnormal blood lipids, and type 2 diabetes by promoting healthy fat storage. Patients carrying such mutations exhibit more normal fat distribution, significantly reduced abdominal fat, improved metabolic conditions, and a decreased risk of cardiovascular diseases and type 2 diabetes [2-4]. These findings suggest that INHBE is a liver-specific negative regulator of fat storage. Inhibiting the expression of INHBE genes and proteins may be a potential strategy for treating metabolic disorders related to improper fat distribution and storage. Consequently, several small nucleic acid pharmaceutical companies, including Alnylam Pharmaceuticals, Arrowhead Pharmaceuticals, and Wave Life Sciences, are currently developing RNA interference (RNAi) drugs targeting INHBE to treat conditions such as obesity [5-7].
RNAi drugs primarily include small interfering RNA (siRNA) and antisense oligonucleotides (ASO). siRNA targets and degrades specific mRNA, while ASO binds to the target mRNA, preventing its translation or inducing its degradation, thereby inhibiting the expression of the target gene. Considering the genetic differences between humans and animals, humanizing mouse genes can accelerate the clinical development of RNAi therapies targeting human INHBE. This strain is a mouse Inhbe gene humanized model and can be used to study therapies targeting INHBE for obesity. The homozygous huINHBE mice are viable and fertile. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen can also generate hot mutation models based on this strain and provide customized services for specific mutations to meet the experimental needs in pharmacology and other fields.
Inhibin βE subunit (INHBE) is a member of the transforming growth factor-β (TGF-β) superfamily, highly specifically expressed in liver cells. The precursor protein of INHBE generates the inhibin β subunit after proteolytic processing. This protein is associated with various cellular processes, including cell proliferation, apoptosis, immune response, and hormone secretion. During the development of obesity and diabetes, the expression of INHBE protein inhibits the proliferation and growth of relevant cells in the pancreas and liver. Research has found a positive correlation between INHBE expression in the liver and insulin resistance and body mass index (BMI), suggesting that INHBE may be a liver factor in altering systemic metabolic status under conditions of obesity-related insulin resistance [1].
The studies conducted by Alnylam Pharmaceuticals and the Regeneron Genetics Center (RGC), respectively, revealed the close relationship between INHBE and fat regulation. The research demonstrated that rare loss-of-function variants in INHBE may protect the liver from the impact of inflammation, abnormal blood lipids, and type 2 diabetes by promoting healthy fat storage. Patients carrying such mutations exhibit more normal fat distribution, significantly reduced abdominal fat, improved metabolic conditions, and a decreased risk of cardiovascular diseases and type 2 diabetes [2-4]. These findings suggest that INHBE is a liver-specific negative regulator of fat storage. Inhibiting the expression of INHBE genes and proteins may be a potential strategy for treating metabolic disorders related to improper fat distribution and storage. Consequently, several small nucleic acid pharmaceutical companies, including Alnylam Pharmaceuticals, Arrowhead Pharmaceuticals, and Wave Life Sciences, are currently developing RNA interference (RNAi) drugs targeting INHBE to treat conditions such as obesity [5-7].
RNAi drugs primarily include small interfering RNA (siRNA) and antisense oligonucleotides (ASO). siRNA targets and degrades specific mRNA, while ASO binds to the target mRNA, preventing its translation or inducing its degradation, thereby inhibiting the expression of the target gene. Considering the genetic differences between humans and animals, humanizing mouse genes can accelerate the clinical development of RNAi therapies targeting human INHBE. This strain is a mouse Inhbe gene humanized model and can be used to study therapies targeting INHBE for obesity. The homozygous huINHBE mice are viable and fertile. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen can also generate hot mutation models based on this strain and provide customized services for specific mutations to meet the experimental needs in pharmacology and other fields.
huINHBE-6xHIS
製品ID :
C002013
系統:
C57BL/6NCya
状況:
説明:
Inhibin βE subunit (INHBE) is a member of the transforming growth factor-β (TGF-β) superfamily and is highly specifically expressed in hepatocytes. The INHBE precursor protein is proteolytically processed to generate the mature inhibin βE subunit, which is involved in various biological processes, including cell proliferation, apoptosis, immune regulation, and hormone secretion. During obesity- and diabetes-associated metabolic disorders, INHBE expression is altered and participates in the regulation of lipid metabolism, adipose storage, and insulin sensitivity. Studies have shown that hepatic INHBE expression is positively correlated with insulin resistance and body mass index (BMI) in humans, suggesting that INHBE may function as a hepatokine involved in systemic metabolic regulation under obesity-associated insulin-resistant conditions [1]. In 2022, studies from Alnylam Pharmaceuticals and the Regeneron Genetics Center (RGC) revealed a close relationship between INHBE and adipose regulation. Research demonstrated that rare loss-of-function (LOF) variants in INHBE may promote healthier adipose storage patterns, improve metabolic profiles, and reduce the risk of obesity-associated inflammation, dyslipidemia, and type 2 diabetes mellitus (T2D). Patients carrying such variants exhibited improved fat distribution, reduced abdominal adiposity, better metabolic health, and significantly decreased risks of cardiovascular disease and T2D [2-4]. These findings indicate that INHBE is a liver-specific negative regulator of adipose storage. Suppression of INHBE expression may represent a potential therapeutic strategy for metabolic disorders associated with abnormal fat distribution and storage. Therefore, several small nucleic acid pharmaceutical companies, including Alnylam Pharmaceuticals, Arrowhead Pharmaceuticals, and Wave Life Sciences, are currently developing RNA interference (RNAi)-based therapeutics targeting INHBE for the treatment of obesity and related metabolic diseases [5-7].
huINHBE-6xHIS mice were generated based on the huINHBE humanized model (Catalog No.: C001533). In this model, the genomic region from the start codon to the 3’UTR of mouse Inhbe was replaced with the corresponding region of human INHBE, and a 6xHIS tag sequence was inserted upstream of the stop codon in exon 2 of the human INHBE gene. This modification enables specific detection of human INHBE protein using His-tag antibodies. The huINHBE-6xHIS mouse model is suitable for investigating the mechanisms of obesity and metabolic diseases, developing therapeutics targeting human INHBE, studying liver-adipose tissue crosstalk, and exploring the pathogenesis of type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD).
Inhibin βE subunit (INHBE) is a member of the transforming growth factor-β (TGF-β) superfamily and is highly specifically expressed in hepatocytes. The INHBE precursor protein is proteolytically processed to generate the mature inhibin βE subunit, which is involved in various biological processes, including cell proliferation, apoptosis, immune regulation, and hormone secretion. During obesity- and diabetes-associated metabolic disorders, INHBE expression is altered and participates in the regulation of lipid metabolism, adipose storage, and insulin sensitivity. Studies have shown that hepatic INHBE expression is positively correlated with insulin resistance and body mass index (BMI) in humans, suggesting that INHBE may function as a hepatokine involved in systemic metabolic regulation under obesity-associated insulin-resistant conditions [1]. In 2022, studies from Alnylam Pharmaceuticals and the Regeneron Genetics Center (RGC) revealed a close relationship between INHBE and adipose regulation. Research demonstrated that rare loss-of-function (LOF) variants in INHBE may promote healthier adipose storage patterns, improve metabolic profiles, and reduce the risk of obesity-associated inflammation, dyslipidemia, and type 2 diabetes mellitus (T2D). Patients carrying such variants exhibited improved fat distribution, reduced abdominal adiposity, better metabolic health, and significantly decreased risks of cardiovascular disease and T2D [2-4]. These findings indicate that INHBE is a liver-specific negative regulator of adipose storage. Suppression of INHBE expression may represent a potential therapeutic strategy for metabolic disorders associated with abnormal fat distribution and storage. Therefore, several small nucleic acid pharmaceutical companies, including Alnylam Pharmaceuticals, Arrowhead Pharmaceuticals, and Wave Life Sciences, are currently developing RNA interference (RNAi)-based therapeutics targeting INHBE for the treatment of obesity and related metabolic diseases [5-7].
huINHBE-6xHIS mice were generated based on the huINHBE humanized model (Catalog No.: C001533). In this model, the genomic region from the start codon to the 3’UTR of mouse Inhbe was replaced with the corresponding region of human INHBE, and a 6xHIS tag sequence was inserted upstream of the stop codon in exon 2 of the human INHBE gene. This modification enables specific detection of human INHBE protein using His-tag antibodies. The huINHBE-6xHIS mouse model is suitable for investigating the mechanisms of obesity and metabolic diseases, developing therapeutics targeting human INHBE, studying liver-adipose tissue crosstalk, and exploring the pathogenesis of type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD).
B6-hINHBE/ob
製品ID :
C001600
系統:
C57BL/6NCya;C57BL/6JCya
状況:
説明:
Inhibin βE subunit (INHBE) is a member of the transforming growth factor-β (TGF-β) superfamily, highly specifically expressed in liver cells. The precursor protein of INHBE generates the inhibin β subunit after proteolytic processing. This protein is associated with various cellular processes, including cell proliferation, apoptosis, immune response, and hormone secretion. During the development of obesity and diabetes, the expression of INHBE protein inhibits the proliferation and growth of relevant cells in the pancreas and liver. Research has found a positive correlation between INHBE expression in the liver and insulin resistance and body mass index (BMI), suggesting that INHBE may be a liver factor in altering systemic metabolic status under conditions of obesity-related insulin resistance [1]. The studies conducted by Alnylam Pharmaceuticals and the Regeneron Genetics Center (RGC), respectively, revealed the close relationship between INHBE and fat regulation. The research demonstrated that rare loss-of-function variants in INHBE may protect the liver from the impact of inflammation, abnormal blood lipids, and type 2 diabetes by promoting healthy fat storage. Patients carrying such mutations exhibit more normal fat distribution, significantly reduced abdominal fat, improved metabolic conditions, and a decreased risk of cardiovascular diseases and type 2 diabetes [2-4]. These findings suggest that INHBE is a liver-specific negative regulator of fat storage. Inhibiting the expression of INHBE genes and proteins may be a potential strategy for treating metabolic disorders related to improper fat distribution and storage. Consequently, several small nucleic acid pharmaceutical companies, including Alnylam Pharmaceuticals, Arrowhead Pharmaceuticals, and Wave Life Sciences, are currently developing RNA interference (RNAi) drugs targeting INHBE to treat obesity [5-7].
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 [8]. 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 [9].
The B6-hINHBE/ob mouse model, generated by mating B6-hINHBE mice (Catalog Number: C001533) with Lep KO (ob/ob) mice (Catalog Number: C001368), is a metabolic disease model. It can be used for research on obesity, type II diabetes, and metabolic diseases related to improper fat distribution and storage, and for the development of human INHBE-targeted therapies.
Inhibin βE subunit (INHBE) is a member of the transforming growth factor-β (TGF-β) superfamily, highly specifically expressed in liver cells. The precursor protein of INHBE generates the inhibin β subunit after proteolytic processing. This protein is associated with various cellular processes, including cell proliferation, apoptosis, immune response, and hormone secretion. During the development of obesity and diabetes, the expression of INHBE protein inhibits the proliferation and growth of relevant cells in the pancreas and liver. Research has found a positive correlation between INHBE expression in the liver and insulin resistance and body mass index (BMI), suggesting that INHBE may be a liver factor in altering systemic metabolic status under conditions of obesity-related insulin resistance [1]. The studies conducted by Alnylam Pharmaceuticals and the Regeneron Genetics Center (RGC), respectively, revealed the close relationship between INHBE and fat regulation. The research demonstrated that rare loss-of-function variants in INHBE may protect the liver from the impact of inflammation, abnormal blood lipids, and type 2 diabetes by promoting healthy fat storage. Patients carrying such mutations exhibit more normal fat distribution, significantly reduced abdominal fat, improved metabolic conditions, and a decreased risk of cardiovascular diseases and type 2 diabetes [2-4]. These findings suggest that INHBE is a liver-specific negative regulator of fat storage. Inhibiting the expression of INHBE genes and proteins may be a potential strategy for treating metabolic disorders related to improper fat distribution and storage. Consequently, several small nucleic acid pharmaceutical companies, including Alnylam Pharmaceuticals, Arrowhead Pharmaceuticals, and Wave Life Sciences, are currently developing RNA interference (RNAi) drugs targeting INHBE to treat obesity [5-7].
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 [8]. 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 [9].
The B6-hINHBE/ob mouse model, generated by mating B6-hINHBE mice (Catalog Number: C001533) with Lep KO (ob/ob) mice (Catalog Number: C001368), is a metabolic disease model. It can be used for research on obesity, type II diabetes, and metabolic diseases related to improper fat distribution and storage, and for the development of human INHBE-targeted therapies.
huINHBC/huINHBE
製品ID :
C001931
系統:
C57BL/6NCya
状況:
説明:
The inhibin βC subunit (INHBC) is a member of the transforming growth factor-β (TGF-β) superfamily. Its encoded precursor protein undergoes hydrolytic processing to form homodimers or heterodimeric activin complexes with βA/βB subunits, which are involved in inhibiting the activin A signaling pathway and regulating multiple physiological processes. INHBC is abundantly expressed in the liver and also participates in the regulation of hormone secretion in the reproductive system [1-2]. Studies have confirmed that circulating INHBC is associated with reduced subcutaneous fat, dyslipidemia, and increased risks of coronary artery disease (CAD) and non-alcoholic fatty liver disease (NAFLD). Meanwhile, obesity, hypertriglyceridemia, type 2 diabetes mellitus, and other conditions positively regulate plasma INHBC levels. Recombinant INHBC (Act-C) can inhibit lipolysis in adipocytes by activating the ALK7-SMAD2/3 signaling pathway, further clarifying its role in metabolic regulation [3].
The inhibin βE subunit (INHBE) is also a member of the TGF-β superfamily, with highly specific expression in hepatocytes. The precursor protein of INHBE generates the inhibin β subunit after proteolytic processing. This protein is associated with various cellular processes, including cell proliferation, apoptosis, immune response, and hormone secretion. During the development of obesity and diabetes, the expression of INHBE protein inhibits the proliferation and growth of relevant cells in the pancreas and liver. Research has found a positive correlation between INHBE expression in the liver and insulin resistance and body mass index (BMI), suggesting that INHBE may be a liver factor in altering systemic metabolic status under conditions of obesity-related insulin resistance [4]. The studies conducted by Alnylam Pharmaceuticals and the Regeneron Genetics Center (RGC) revealed the close relationship between INHBE and fat regulation. The research demonstrated that rare loss-of-function variants in INHBE may protect the liver from the impact of inflammation, abnormal blood lipids, and type 2 diabetes by promoting healthy fat storage. Patients carrying such mutations exhibit more normal fat distribution, significantly reduced abdominal fat, improved metabolic conditions, and a decreased risk of cardiovascular diseases and type 2 diabetes [5-7]. These findings suggest that INHBE is a liver-specific negative regulator of fat storage. Inhibiting the expression of INHBE genes and proteins may be a promising strategy for treating metabolic disorders associated with improper fat distribution and storage.
The huINHBC/huINHBE mouse is a dual-gene humanized model established via gene editing technology. In this model, the sequences from upstream of the mouse Inhbc exon 1 to the mouse Inhbe 3'UTR were replaced with the sequences from upstream of the human INHBC exon 1 to 3'UTR of the human INHBE. This model can be utilized for investigating the mechanisms and therapeutic approaches of fat distribution and storage, dyslipidemia, CAD, NAFLD, as well as for the development of INHBC/INHBE-targeted drugs.
The inhibin βC subunit (INHBC) is a member of the transforming growth factor-β (TGF-β) superfamily. Its encoded precursor protein undergoes hydrolytic processing to form homodimers or heterodimeric activin complexes with βA/βB subunits, which are involved in inhibiting the activin A signaling pathway and regulating multiple physiological processes. INHBC is abundantly expressed in the liver and also participates in the regulation of hormone secretion in the reproductive system [1-2]. Studies have confirmed that circulating INHBC is associated with reduced subcutaneous fat, dyslipidemia, and increased risks of coronary artery disease (CAD) and non-alcoholic fatty liver disease (NAFLD). Meanwhile, obesity, hypertriglyceridemia, type 2 diabetes mellitus, and other conditions positively regulate plasma INHBC levels. Recombinant INHBC (Act-C) can inhibit lipolysis in adipocytes by activating the ALK7-SMAD2/3 signaling pathway, further clarifying its role in metabolic regulation [3].
The inhibin βE subunit (INHBE) is also a member of the TGF-β superfamily, with highly specific expression in hepatocytes. The precursor protein of INHBE generates the inhibin β subunit after proteolytic processing. This protein is associated with various cellular processes, including cell proliferation, apoptosis, immune response, and hormone secretion. During the development of obesity and diabetes, the expression of INHBE protein inhibits the proliferation and growth of relevant cells in the pancreas and liver. Research has found a positive correlation between INHBE expression in the liver and insulin resistance and body mass index (BMI), suggesting that INHBE may be a liver factor in altering systemic metabolic status under conditions of obesity-related insulin resistance [4]. The studies conducted by Alnylam Pharmaceuticals and the Regeneron Genetics Center (RGC) revealed the close relationship between INHBE and fat regulation. The research demonstrated that rare loss-of-function variants in INHBE may protect the liver from the impact of inflammation, abnormal blood lipids, and type 2 diabetes by promoting healthy fat storage. Patients carrying such mutations exhibit more normal fat distribution, significantly reduced abdominal fat, improved metabolic conditions, and a decreased risk of cardiovascular diseases and type 2 diabetes [5-7]. These findings suggest that INHBE is a liver-specific negative regulator of fat storage. Inhibiting the expression of INHBE genes and proteins may be a promising strategy for treating metabolic disorders associated with improper fat distribution and storage.
The huINHBC/huINHBE mouse is a dual-gene humanized model established via gene editing technology. In this model, the sequences from upstream of the mouse Inhbc exon 1 to the mouse Inhbe 3'UTR were replaced with the sequences from upstream of the human INHBC exon 1 to 3'UTR of the human INHBE. This model can be utilized for investigating the mechanisms and therapeutic approaches of fat distribution and storage, dyslipidemia, CAD, NAFLD, as well as for the development of INHBC/INHBE-targeted drugs.
huGDF8/huINHBE
製品ID :
C002074
系統:
C57BL/6NCya
状況:
説明:
The huGDF8/huINHBE mouse is a dual-gene humanized model obtained by crossing the huMSTN(GDF8) mouse (Catalog No.: C001636) with the huINHBE mouse (Catalog No.: C001533). The huGDF8/huINHBE mouse is a dual-target humanized model that integrates skeletal muscle growth regulation with lipid metabolism control. Co-expressing humanized MSTN and INHBE genes, this model can be utilized for the screening, pharmacodynamic evaluation, safety assessment, and mechanism of action studies of dual-target therapeutics targeting MSTN and INHBE. It serves as an ideal preclinical research platform for developing innovative therapies for diseases including obesity, sarcopenic obesity, and metabolic syndrome.
The huGDF8/huINHBE mouse is a dual-gene humanized model obtained by crossing the huMSTN(GDF8) mouse (Catalog No.: C001636) with the huINHBE mouse (Catalog No.: C001533). The huGDF8/huINHBE mouse is a dual-target humanized model that integrates skeletal muscle growth regulation with lipid metabolism control. Co-expressing humanized MSTN and INHBE genes, this model can be utilized for the screening, pharmacodynamic evaluation, safety assessment, and mechanism of action studies of dual-target therapeutics targeting MSTN and INHBE. It serves as an ideal preclinical research platform for developing innovative therapies for diseases including obesity, sarcopenic obesity, and metabolic syndrome.
huALK7/huINHBE
製品ID :
C001994
系統:
C57BL/6NCya
状況:
説明:
The huALK7/huINHBE mice are a dual-gene humanized model obtained by mating the huALK7(ACVR1C) mice (catalog number: C001911) with the huINHBE mice (catalog number: C001533). This model can be used for the research on pathological mechanisms and treatment methods of metabolic diseases such as obesity and type 2 diabetes (T2D), as well as malignant tumors such as retinoblastoma. It can also be used for the screening, development, and safety evaluation of ACVR1C/INHBE-targeted drugs.
The huALK7/huINHBE mice are a dual-gene humanized model obtained by mating the huALK7(ACVR1C) mice (catalog number: C001911) with the huINHBE mice (catalog number: C001533). This model can be used for the research on pathological mechanisms and treatment methods of metabolic diseases such as obesity and type 2 diabetes (T2D), as well as malignant tumors such as retinoblastoma. It can also be used for the screening, development, and safety evaluation of ACVR1C/INHBE-targeted drugs.
huINHBE/huCIDEB(2)
製品ID :
C002025
系統:
C57BL/6N;6JCya
状況:
説明:
The huINHBE/huCIDEB(2) mice are a double-gene humanized model obtained by mating huINHBE mice (Catalog Number: C001533) with huCIDEB(2) mice (Catalog Number: C001990). This model is applicable to the study of pathogenesis of various liver diseases, such as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), Metabolic Dysfunction-Associated Steatohepatitis (MASH), cirrhosis, and viral hepatitis (HCV, HBV), as well as the research on obesity and metabolic diseases associated with improper fat distribution and storage. It can also be used for the screening, development, and preclinical evaluation of INHBE/CIDEB-targeted therapeutics.
The huINHBE/huCIDEB(2) mice are a double-gene humanized model obtained by mating huINHBE mice (Catalog Number: C001533) with huCIDEB(2) mice (Catalog Number: C001990). This model is applicable to the study of pathogenesis of various liver diseases, such as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), Metabolic Dysfunction-Associated Steatohepatitis (MASH), cirrhosis, and viral hepatitis (HCV, HBV), as well as the research on obesity and metabolic diseases associated with improper fat distribution and storage. It can also be used for the screening, development, and preclinical evaluation of INHBE/CIDEB-targeted therapeutics.
huPCSK9/huINHBE
製品ID :
C002095
系統:
C57BL/6NCya
状況:
説明:
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease primarily produced by the liver and also expressed in the intestine, heart, pancreas, renal interstitial cells, and neurons. The N-terminal domain of the PCSK9 protein is responsible for protein localization and stability, while the C-terminal domain mediates enzymatic activity [1]. PCSK9 is closely involved in the regulation of circulating cholesterol. Low-density lipoprotein receptor (LDLR) clears low-density lipoprotein cholesterol (LDL-C) from the blood. PCSK9 binds to and cleaves the intracellular domain of cell-surface LDLR, promoting its shedding from the plasma membrane and subsequent trafficking to lysosomes for degradation, thereby elevating plasma LDL-C levels. Overexpression of the PCSK9 gene or gain-of-function mutations reduce LDLR levels, leading to LDL-C accumulation, hypercholesterolemia, and increased risk of cardiovascular diseases such as atherosclerosis and coronary heart disease, as well as stroke and neurodegenerative diseases including Alzheimer’s disease (AD) [2].
Inhibin βE subunit (INHBE) is a member of the transforming growth factor-β (TGF-β) superfamily and is highly specifically expressed in hepatocytes. After proteolytic processing of the INHBE precursor, the inhibin β subunit is generated and participates in multiple cellular processes, including proliferation, apoptosis, immune responses, and hormone secretion. During the development of obesity and diabetes, INHBE protein expression can suppress the proliferation and growth of relevant cells in the pancreas and liver. Studies have shown that hepatic INHBE expression is positively correlated with insulin resistance and body mass index (BMI) in humans, suggesting that INHBE may act as a hepatic factor that alters systemic metabolic status under conditions of obesity-associated insulin resistance [3]. In addition, rare loss-of-function (LOF) mutations in INHBE may protect the liver from inflammation, dyslipidemia, and type 2 diabetes (T2D) by promoting healthy fat storage. Carriers of such mutations exhibit more normal fat distribution, markedly reduced abdominal fat, favorable metabolic profiles, and significantly lower risks of cardiovascular disease and type 2 diabetes (T2D) [4-6]. These findings indicate that INHBE is a liver-specific negative regulator of fat storage, and that inhibition of INHBE gene and protein expression may represent a potential therapeutic strategy for metabolic diseases associated with improper fat distribution and storage.
huPCSK9/huINHBE mice are dual-gene humanized models generated by crossing huPCSK9 mice (Catalog No.: C001617) with huINHBE mice (Catalog No.: C001533). These models can be used for screening, pharmacodynamic evaluation, safety assessment, and mechanism-of-action studies of dual-target drugs against PCSK9/INHBE, providing an ideal preclinical research platform for the development of innovative therapies for lipid metabolism disorder-related metabolic diseases, including hypercholesterolemia, atherosclerosis, obesity, and type 2 diabetes (T2D).
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease primarily produced by the liver and also expressed in the intestine, heart, pancreas, renal interstitial cells, and neurons. The N-terminal domain of the PCSK9 protein is responsible for protein localization and stability, while the C-terminal domain mediates enzymatic activity [1]. PCSK9 is closely involved in the regulation of circulating cholesterol. Low-density lipoprotein receptor (LDLR) clears low-density lipoprotein cholesterol (LDL-C) from the blood. PCSK9 binds to and cleaves the intracellular domain of cell-surface LDLR, promoting its shedding from the plasma membrane and subsequent trafficking to lysosomes for degradation, thereby elevating plasma LDL-C levels. Overexpression of the PCSK9 gene or gain-of-function mutations reduce LDLR levels, leading to LDL-C accumulation, hypercholesterolemia, and increased risk of cardiovascular diseases such as atherosclerosis and coronary heart disease, as well as stroke and neurodegenerative diseases including Alzheimer’s disease (AD) [2].
Inhibin βE subunit (INHBE) is a member of the transforming growth factor-β (TGF-β) superfamily and is highly specifically expressed in hepatocytes. After proteolytic processing of the INHBE precursor, the inhibin β subunit is generated and participates in multiple cellular processes, including proliferation, apoptosis, immune responses, and hormone secretion. During the development of obesity and diabetes, INHBE protein expression can suppress the proliferation and growth of relevant cells in the pancreas and liver. Studies have shown that hepatic INHBE expression is positively correlated with insulin resistance and body mass index (BMI) in humans, suggesting that INHBE may act as a hepatic factor that alters systemic metabolic status under conditions of obesity-associated insulin resistance [3]. In addition, rare loss-of-function (LOF) mutations in INHBE may protect the liver from inflammation, dyslipidemia, and type 2 diabetes (T2D) by promoting healthy fat storage. Carriers of such mutations exhibit more normal fat distribution, markedly reduced abdominal fat, favorable metabolic profiles, and significantly lower risks of cardiovascular disease and type 2 diabetes (T2D) [4-6]. These findings indicate that INHBE is a liver-specific negative regulator of fat storage, and that inhibition of INHBE gene and protein expression may represent a potential therapeutic strategy for metabolic diseases associated with improper fat distribution and storage.
huPCSK9/huINHBE mice are dual-gene humanized models generated by crossing huPCSK9 mice (Catalog No.: C001617) with huINHBE mice (Catalog No.: C001533). These models can be used for screening, pharmacodynamic evaluation, safety assessment, and mechanism-of-action studies of dual-target drugs against PCSK9/INHBE, providing an ideal preclinical research platform for the development of innovative therapies for lipid metabolism disorder-related metabolic diseases, including hypercholesterolemia, atherosclerosis, obesity, and type 2 diabetes (T2D).
huGDF8/huALK7/huINHBE
製品ID :
C002082
系統:
C57BL/6NCya
状況:
説明:
Growth differentiation factor 8 (GDF8) is a key negative regulator of skeletal muscle growth that inhibits the proliferation and differentiation of muscle cells and maintains muscle mass homeostasis [1-4]. Activin receptor-like kinase 7 (ALK7, ACVR1C) is a type I receptor of the transforming growth factor-β (TGF-β) superfamily. It is widely expressed in adipose tissue and metabolically active organs and participates in the regulation of adipogenesis, energy metabolism, and glucose homeostasis [5-6]. Inhibin beta E subunit (INHBE) is a liver-specific member of the TGF-β superfamily. The Activin E encoded by INHBE functions as a hepatokine that plays an important role in maintaining metabolic homeostasis by regulating lipid storage, adipose tissue function, and systemic energy metabolism [7]. Recent studies have further demonstrated that the INHBE-ALK7 signaling axis participates in the metabolic regulation between the liver and adipose tissue, and its dysregulation is closely associated with metabolic diseases, including obesity, type 2 diabetes (T2D), and metabolic dysfunction-associated steatotic liver disease (MASLD) [8]. Meanwhile, GDF8-mediated regulation of skeletal muscle mass is extensively interconnected with adipose and hepatic metabolism [9-10]. GDF8, INHBE, and ALK7 each participate in the metabolic regulation among these tissues and collectively influence whole-body energy homeostasis, fat distribution, and glucose metabolism, providing new insights into combination intervention strategies for promoting muscle growth, reducing adiposity, and improving metabolic health.
The huGDF8/huALK7/huINHBE mouse is a triple-gene humanized model that can be generated by intercrossing the huMSTN(GDF8) mouse (Catalog No.: C001636), the huALK7(ACVR1C) mice (Catalog No.: C001911) and the huINHBE mice (Catalog No.: C001533). This model simultaneously carries the humanized GDF8, ACVR1C, and INHBE genes and can be used for the screening, pharmacodynamic evaluation, safety assessment, and mechanism of action studies of therapeutics targeting GDF8, ACVR1C, and INHBE, as well as studies on body composition remodeling, regulation of the muscle-adipose-liver metabolic axis, and energy metabolic reprogramming. It also serves as a preclinical research platform for developing combination therapeutic strategies for promoting muscle growth, reducing adiposity, and improving metabolic health, as well as innovative therapies for metabolic diseases, including obesity, type 2 diabetes (T2D), and metabolic dysfunction-associated steatotic liver disease (MASLD).
Growth differentiation factor 8 (GDF8) is a key negative regulator of skeletal muscle growth that inhibits the proliferation and differentiation of muscle cells and maintains muscle mass homeostasis [1-4]. Activin receptor-like kinase 7 (ALK7, ACVR1C) is a type I receptor of the transforming growth factor-β (TGF-β) superfamily. It is widely expressed in adipose tissue and metabolically active organs and participates in the regulation of adipogenesis, energy metabolism, and glucose homeostasis [5-6]. Inhibin beta E subunit (INHBE) is a liver-specific member of the TGF-β superfamily. The Activin E encoded by INHBE functions as a hepatokine that plays an important role in maintaining metabolic homeostasis by regulating lipid storage, adipose tissue function, and systemic energy metabolism [7]. Recent studies have further demonstrated that the INHBE-ALK7 signaling axis participates in the metabolic regulation between the liver and adipose tissue, and its dysregulation is closely associated with metabolic diseases, including obesity, type 2 diabetes (T2D), and metabolic dysfunction-associated steatotic liver disease (MASLD) [8]. Meanwhile, GDF8-mediated regulation of skeletal muscle mass is extensively interconnected with adipose and hepatic metabolism [9-10]. GDF8, INHBE, and ALK7 each participate in the metabolic regulation among these tissues and collectively influence whole-body energy homeostasis, fat distribution, and glucose metabolism, providing new insights into combination intervention strategies for promoting muscle growth, reducing adiposity, and improving metabolic health.
The huGDF8/huALK7/huINHBE mouse is a triple-gene humanized model that can be generated by intercrossing the huMSTN(GDF8) mouse (Catalog No.: C001636), the huALK7(ACVR1C) mice (Catalog No.: C001911) and the huINHBE mice (Catalog No.: C001533). This model simultaneously carries the humanized GDF8, ACVR1C, and INHBE genes and can be used for the screening, pharmacodynamic evaluation, safety assessment, and mechanism of action studies of therapeutics targeting GDF8, ACVR1C, and INHBE, as well as studies on body composition remodeling, regulation of the muscle-adipose-liver metabolic axis, and energy metabolic reprogramming. It also serves as a preclinical research platform for developing combination therapeutic strategies for promoting muscle growth, reducing adiposity, and improving metabolic health, as well as innovative therapies for metabolic diseases, including obesity, type 2 diabetes (T2D), and metabolic dysfunction-associated steatotic liver disease (MASLD).
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