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Alpl KO
Product ID:
C001849
Strain:
C57BL/6JCya
Status:
Description:
The ALPL gene encodes for the tissue-nonspecific alkaline phosphatase (TNSALP) enzyme, a membrane-bound glycoprotein. This enzyme is expressed in a variety of cellular tissues, most notably in the liver, bone, and kidney, as well as in other areas like teeth and mesenchymal stem cells [1]. Its primary function is to act as a hydrolase, removing phosphate groups from molecules. This is a critical function for skeletal and dental mineralization, where it hydrolyzes inorganic pyrophosphate (a mineralization inhibitor) into phosphate, which then combines with calcium to form bone [2]. Mutations in the ALPL gene lead to hypophosphatasia (HPP), a rare inherited metabolic disease characterized by defective bone and tooth mineralization, rickets, osteomalacia, and in severe cases, seizures and respiratory complications. The severity of HPP varies, ranging from mild forms with dental issues to life-threatening perinatal forms [3]. Variations in the ALPL gene may also be associated with other diseases, such as osteoporosis. Research has found a high frequency of homozygous common ALPL gene variants in adult patients with atypical femoral fractures or with biochemical/clinical signs of hypophosphatasia (HPP). This suggests that variations in the ALPL gene may be linked to an increased risk of these fractures [4]. Furthermore, the expression and function of the ALPL gene may be relevant to cancer immunotherapy. Studies have shown that an alkaline phosphatase isoform, known as ALPL-1, is highly expressed in osteosarcoma (OS) [5].
The Alpl KO mouse is a knockout (KO) model in which the exon 3~4 of the Alpl gene (homologous to the human ALPL gene) has been deleted via gene-editing technology. Preliminary validation data indicate that homozygous Alpl KO mice have a short lifespan, dying within four weeks when given a specialized diet. If they are not provided with this dietary support, no surviving homozygous individuals are obtained. This model can be used to study the pathogenic mechanisms of diseases such as hypophosphatasia (HPP), osteoporosis, and osteosarcoma (OS), and to provide a basis for developing related therapeutic strategies.
The ALPL gene encodes for the tissue-nonspecific alkaline phosphatase (TNSALP) enzyme, a membrane-bound glycoprotein. This enzyme is expressed in a variety of cellular tissues, most notably in the liver, bone, and kidney, as well as in other areas like teeth and mesenchymal stem cells [1]. Its primary function is to act as a hydrolase, removing phosphate groups from molecules. This is a critical function for skeletal and dental mineralization, where it hydrolyzes inorganic pyrophosphate (a mineralization inhibitor) into phosphate, which then combines with calcium to form bone [2]. Mutations in the ALPL gene lead to hypophosphatasia (HPP), a rare inherited metabolic disease characterized by defective bone and tooth mineralization, rickets, osteomalacia, and in severe cases, seizures and respiratory complications. The severity of HPP varies, ranging from mild forms with dental issues to life-threatening perinatal forms [3]. Variations in the ALPL gene may also be associated with other diseases, such as osteoporosis. Research has found a high frequency of homozygous common ALPL gene variants in adult patients with atypical femoral fractures or with biochemical/clinical signs of hypophosphatasia (HPP). This suggests that variations in the ALPL gene may be linked to an increased risk of these fractures [4]. Furthermore, the expression and function of the ALPL gene may be relevant to cancer immunotherapy. Studies have shown that an alkaline phosphatase isoform, known as ALPL-1, is highly expressed in osteosarcoma (OS) [5].
The Alpl KO mouse is a knockout (KO) model in which the exon 3~4 of the Alpl gene (homologous to the human ALPL gene) has been deleted via gene-editing technology. Preliminary validation data indicate that homozygous Alpl KO mice have a short lifespan, dying within four weeks when given a specialized diet. If they are not provided with this dietary support, no surviving homozygous individuals are obtained. This model can be used to study the pathogenic mechanisms of diseases such as hypophosphatasia (HPP), osteoporosis, and osteosarcoma (OS), and to provide a basis for developing related therapeutic strategies.
Agxt KO
Product ID:
C001703
Strain:
C57BL/6NCya
Status:
Description:
The AGXT gene, mapping to chromosome 2q37.3, encodes alanine-glyoxylate aminotransferase (AGT), a pyridoxal 5'-phosphate-dependent homotetrameric enzyme predominantly expressed in hepatic peroxisomes [1]. AGT is central to glyoxylate metabolism, catalyzing its transamination to glycine and preventing its oxidation to oxalate [1]. Primary Hyperoxaluria Type 1 (PH1), a rare autosomal recessive disorder affecting approximately 1-3 per million individuals, arises from over 175 identified pathogenic mutations in AGXT. These mutations typically result in deficient or mislocalized AGT, leading to marked overproduction of oxalate [2]. The ensuing hyperoxaluria causes deposition of calcium oxalate in the kidneys, manifesting as nephrolithiasis and nephrocalcinosis, which can progress to end-stage renal disease [3]. In severe cases, systemic oxalosis can occur [4]. Agxt-deficient mice serve as critical preclinical models, faithfully mirroring the biochemical and pathological features of PH1 and enabling the evaluation of diverse therapeutic modalities, including enzyme replacement, substrate reduction, and gene therapy.
The Agxt KO mouse is a gene knockout model created using gene-editing techniques to knock out the coding sequence of the Agxt gene (the homolog of the human AGXT gene) in mice. This model is used to research the pathogenic mechanisms of primary hyperoxaluria and develop related therapeutic strategies.
The AGXT gene, mapping to chromosome 2q37.3, encodes alanine-glyoxylate aminotransferase (AGT), a pyridoxal 5'-phosphate-dependent homotetrameric enzyme predominantly expressed in hepatic peroxisomes [1]. AGT is central to glyoxylate metabolism, catalyzing its transamination to glycine and preventing its oxidation to oxalate [1]. Primary Hyperoxaluria Type 1 (PH1), a rare autosomal recessive disorder affecting approximately 1-3 per million individuals, arises from over 175 identified pathogenic mutations in AGXT. These mutations typically result in deficient or mislocalized AGT, leading to marked overproduction of oxalate [2]. The ensuing hyperoxaluria causes deposition of calcium oxalate in the kidneys, manifesting as nephrolithiasis and nephrocalcinosis, which can progress to end-stage renal disease [3]. In severe cases, systemic oxalosis can occur [4]. Agxt-deficient mice serve as critical preclinical models, faithfully mirroring the biochemical and pathological features of PH1 and enabling the evaluation of diverse therapeutic modalities, including enzyme replacement, substrate reduction, and gene therapy.
The Agxt KO mouse is a gene knockout model created using gene-editing techniques to knock out the coding sequence of the Agxt gene (the homolog of the human AGXT gene) in mice. This model is used to research the pathogenic mechanisms of primary hyperoxaluria and develop related therapeutic strategies.
Atp7b-KO
Product ID:
C001267
Strain:
C57BL/6NCya
Status:
Description:
The ATP7B gene encodes a copper-transporting ATPase β-peptide that is a member of the P-type cation-transporting ATPase family, which uses the energy stored in adenosine triphosphate (ATP) molecules to transport metals into and out of cells. The ATP7B protein consists of multiple transmembrane structural domains, an ATPase consensus sequence, a hinge structural domain, and a phosphorylation site, as well as at least two putative copper-binding sites [1]. This protein is found mainly in the liver and to a lesser extent in the kidney and brain, and functions as a copper-transporting ATPase that plays a role in transporting copper from the liver to other parts of the body. Copper is an important component of certain enzymes that maintain normal cellular function, and the ATP7B protein is important for the removal of excess copper from the body. Mutations in this gene are associated with Wilson disease (WD), which is characterized by the accumulation of copper to toxic levels that damage tissues and organs such as the liver and brain as the removal of excess copper from the body is compromised with the absence of the functional ATP7B protein [2-4].
This strain is an Atp7b deletion mouse model, which uses gene editing technology to knock out Atp7b, the homolog of the human ATP7B gene in mice that lack the expression of ATP7B protein and can be used in the study of disorders related to copper metabolisms such as Wilson's disease, acute liver failure, and steatohepatitis. The heterozygous Atp7b KO mice are viable and fertile, and homozygous mice have a reduced life expectancy.
The ATP7B gene encodes a copper-transporting ATPase β-peptide that is a member of the P-type cation-transporting ATPase family, which uses the energy stored in adenosine triphosphate (ATP) molecules to transport metals into and out of cells. The ATP7B protein consists of multiple transmembrane structural domains, an ATPase consensus sequence, a hinge structural domain, and a phosphorylation site, as well as at least two putative copper-binding sites [1]. This protein is found mainly in the liver and to a lesser extent in the kidney and brain, and functions as a copper-transporting ATPase that plays a role in transporting copper from the liver to other parts of the body. Copper is an important component of certain enzymes that maintain normal cellular function, and the ATP7B protein is important for the removal of excess copper from the body. Mutations in this gene are associated with Wilson disease (WD), which is characterized by the accumulation of copper to toxic levels that damage tissues and organs such as the liver and brain as the removal of excess copper from the body is compromised with the absence of the functional ATP7B protein [2-4].
This strain is an Atp7b deletion mouse model, which uses gene editing technology to knock out Atp7b, the homolog of the human ATP7B gene in mice that lack the expression of ATP7B protein and can be used in the study of disorders related to copper metabolisms such as Wilson's disease, acute liver failure, and steatohepatitis. The heterozygous Atp7b KO mice are viable and fertile, and homozygous mice have a reduced life expectancy.
Abca4/Rdh8-DKO
Product ID:
C001968
Strain:
C57BL/6JCya
Status:
Description:
The Abca4/Rdh8-DKO mouse is a dual-gene knockout model obtained by mating Rdh8-KO mice (catalog No.: C001969) with Abca4-KO mice (catalog No.: C002024). This model can be used to investigate the pathogenic mechanisms and therapeutic strategies of diseases, including Stargardt disease (STGD) and age‑related macular degeneration (AMD), and facilitates the evaluation of synergistic effects of polygenic therapies.
The Abca4/Rdh8-DKO mouse is a dual-gene knockout model obtained by mating Rdh8-KO mice (catalog No.: C001969) with Abca4-KO mice (catalog No.: C002024). This model can be used to investigate the pathogenic mechanisms and therapeutic strategies of diseases, including Stargardt disease (STGD) and age‑related macular degeneration (AMD), and facilitates the evaluation of synergistic effects of polygenic therapies.
Abca4-KO
Product ID:
C002024
Strain:
C57BL/6JCya
Status:
Description:
Stargardt disease (STGD), a hereditary macular dystrophy, is characterized by the presence of yellowish flecks within the retinal pigment epithelium (RPE), ultimately culminating in macular atrophy. Typically manifesting in childhood and adolescence, STGD leads to progressive central vision loss and mild dyschromatopsia. Fundoscopic examination may reveal pale yellow lesions exhibiting a characteristic gold foil-like sheen, accompanied by yellow-white spots surrounding the posterior pole. In advanced stages, atrophy of the RPE, photoreceptors, and choriocapillaris is observed. This bilateral and typically synchronous condition affects both eyes with comparable incidence across sexes, estimated between 1/8,000 and 1/13,000. STGD is predominantly an autosomal recessive disorder, with mutations in the ABCA4 gene accounting for approximately 95% of cases. ABCA4 encodes a retina-specific ABC transporter protein crucial for the clearance of retinal derivatives and toxic metabolites generated during rhodopsin photobleaching. Consequently, ABCA4 mutations result in the accumulation of these cytotoxic substances, triggering apoptosis of both RPE and photoreceptor cells and ultimately driving retinal degeneration. Notably, ABCA4 mutations have been implicated in a spectrum of retinal diseases, including STGD, cone-rod dystrophy (CRD), age-related macular degeneration (AMD), and retinitis pigmentosa (RP), with the specific clinical phenotype correlating with the nature and severity of the ABCA4 mutation.
This strain is an Abca4 gene knockout (KO) mouse model. Gene-editing technology was used to delete the protein-coding sequence of the Abca4 gene (the homolog of the human ABCA4 gene) in mice. Previous studies have demonstrated that Abca4 KO mice exhibit delayed dark adaptation following photobleaching and a slow progression of photoreceptor degeneration[1]. Homozygous Abca4-KO mice are viable and fertile.
Stargardt disease (STGD), a hereditary macular dystrophy, is characterized by the presence of yellowish flecks within the retinal pigment epithelium (RPE), ultimately culminating in macular atrophy. Typically manifesting in childhood and adolescence, STGD leads to progressive central vision loss and mild dyschromatopsia. Fundoscopic examination may reveal pale yellow lesions exhibiting a characteristic gold foil-like sheen, accompanied by yellow-white spots surrounding the posterior pole. In advanced stages, atrophy of the RPE, photoreceptors, and choriocapillaris is observed. This bilateral and typically synchronous condition affects both eyes with comparable incidence across sexes, estimated between 1/8,000 and 1/13,000. STGD is predominantly an autosomal recessive disorder, with mutations in the ABCA4 gene accounting for approximately 95% of cases. ABCA4 encodes a retina-specific ABC transporter protein crucial for the clearance of retinal derivatives and toxic metabolites generated during rhodopsin photobleaching. Consequently, ABCA4 mutations result in the accumulation of these cytotoxic substances, triggering apoptosis of both RPE and photoreceptor cells and ultimately driving retinal degeneration. Notably, ABCA4 mutations have been implicated in a spectrum of retinal diseases, including STGD, cone-rod dystrophy (CRD), age-related macular degeneration (AMD), and retinitis pigmentosa (RP), with the specific clinical phenotype correlating with the nature and severity of the ABCA4 mutation.
This strain is an Abca4 gene knockout (KO) mouse model. Gene-editing technology was used to delete the protein-coding sequence of the Abca4 gene (the homolog of the human ABCA4 gene) in mice. Previous studies have demonstrated that Abca4 KO mice exhibit delayed dark adaptation following photobleaching and a slow progression of photoreceptor degeneration[1]. Homozygous Abca4-KO mice are viable and fertile.
B6-Rpe65 R44X
Product ID:
C001360
Strain:
C57BL/6JCya
Status:
Description:
Leber congenital amaurosis (LCA) is a group of inherited retinal diseases accompanied by severe visual impairment. The main symptoms of this disease are vision loss at birth or within a few months after birth, nystagmus, and weakened or absent light reflexes of rods and cones. Approximately 16% of LCA cases are caused by mutations in the RPE65 gene. In visual cells, vitamin A aldehyde (retinal) combines with opsin to form visual pigments. After vitamin A aldehyde absorbs light, it is isomerized to all - trans - retinal, which causes a conformational change in rhodopsin and initiates nerve impulses to the brain, thus forming vision. During the decomposition and resynthesis of rhodopsin, a portion of vitamin A aldehyde is consumed and is mainly replenished by vitamin A (retinol) in the blood.The retinoid isomerase encoded by the RPE65 gene is present in the retinal pigment epithelial cells (RPE) of the retina. The RPE65 protein plays a crucial role in the visual process. It participates in the conversion of vitamin A to vitamin A aldehyde and the regeneration of retinal photoreceptor pigments, so it is a key molecule for the conversion and transmission of light signals in the retina[1].
Mutations in the RPE65 gene can lead to further degeneration of the neural retina and RPE cells, resulting in irreversible blindness. Multiple allelic mutations of RPE65 have been found to damage optic nerve cells and cause type II Leber congenital amaurosis (LCA2) and early - onset severe retinal atrophy (EOSRD), ultimately leading to complete blindness[1-3].
This model is a mouse Rpe65 gene point - mutation model. Using gene - editing technology, a p.R44*(CGA to TGA) point mutation was introduced into the mouse Rpe65 gene, which led to abnormal expression of the mouse Rpe65 protein. This caused phenotypes such as damage to RPE cell function, apoptosis of photoreceptor cells, disordered arrangement of rod outer segment membrane discs, and extinction of rod waveforms, resulting in severe retinal degeneration.
This model is a mouse Rpe65 gene point - mutation model. Using gene - editing technology, a p.R44*(CGA to TGA) point mutation was introduced into the mouse Rpe65 gene, which led to abnormal expression of the mouse Rpe65 protein. This caused phenotypes such as damage to RPE cell function, apoptosis of photoreceptor cells, disordered arrangement of rod outer segment membrane discs, and extinction of rod waveforms, resulting in severe retinal degeneration.
Leber congenital amaurosis (LCA) is a group of inherited retinal diseases accompanied by severe visual impairment. The main symptoms of this disease are vision loss at birth or within a few months after birth, nystagmus, and weakened or absent light reflexes of rods and cones. Approximately 16% of LCA cases are caused by mutations in the RPE65 gene. In visual cells, vitamin A aldehyde (retinal) combines with opsin to form visual pigments. After vitamin A aldehyde absorbs light, it is isomerized to all - trans - retinal, which causes a conformational change in rhodopsin and initiates nerve impulses to the brain, thus forming vision. During the decomposition and resynthesis of rhodopsin, a portion of vitamin A aldehyde is consumed and is mainly replenished by vitamin A (retinol) in the blood.The retinoid isomerase encoded by the RPE65 gene is present in the retinal pigment epithelial cells (RPE) of the retina. The RPE65 protein plays a crucial role in the visual process. It participates in the conversion of vitamin A to vitamin A aldehyde and the regeneration of retinal photoreceptor pigments, so it is a key molecule for the conversion and transmission of light signals in the retina[1].
Mutations in the RPE65 gene can lead to further degeneration of the neural retina and RPE cells, resulting in irreversible blindness. Multiple allelic mutations of RPE65 have been found to damage optic nerve cells and cause type II Leber congenital amaurosis (LCA2) and early - onset severe retinal atrophy (EOSRD), ultimately leading to complete blindness[1-3].
This model is a mouse Rpe65 gene point - mutation model. Using gene - editing technology, a p.R44*(CGA to TGA) point mutation was introduced into the mouse Rpe65 gene, which led to abnormal expression of the mouse Rpe65 protein. This caused phenotypes such as damage to RPE cell function, apoptosis of photoreceptor cells, disordered arrangement of rod outer segment membrane discs, and extinction of rod waveforms, resulting in severe retinal degeneration.
This model is a mouse Rpe65 gene point - mutation model. Using gene - editing technology, a p.R44*(CGA to TGA) point mutation was introduced into the mouse Rpe65 gene, which led to abnormal expression of the mouse Rpe65 protein. This caused phenotypes such as damage to RPE cell function, apoptosis of photoreceptor cells, disordered arrangement of rod outer segment membrane discs, and extinction of rod waveforms, resulting in severe retinal degeneration.
B6-hMECP2*T158M
Product ID:
C001569
Strain:
C57BL/6NCya
Status:
Description:
Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder primarily affecting female infants and young children, with an incidence of approximately 1 in 10,000 to 15,000 females. Characteristic clinical features include intellectual disability, loss of language skills, stereotypic hand movements, and gait disturbances. Affected individuals typically experience a period of normal development, followed by deceleration in head circumference growth between 6 to 18 months of age, and subsequent regression of acquired motor and cognitive abilities. Overt impairments in cognition and motor function generally emerge within 1 to 2 years. Mutations in the methyl-CpG-binding protein 2 (MECP2) gene are responsible for over 90% of RTT cases. MECP2 is a nuclear protein that binds methylated DNA to modulate gene transcription. MECP2 gene duplications lead to MECP2 duplication syndrome (MDS), while MECP2 deficiency disrupts central nervous system maturation, adversely affecting learning and memory, culminating in the clinical manifestations of RTT.
Current therapeutic strategies for RTT primarily revolve around gene supplementation using adeno-associated virus (AAV) vectors to deliver functional human MECP2 genes to compensate for the endogenous deficiency. However, the substantial size of the MECP2 gene surpasses the packaging capacity of most viral vectors, and overexpression of MECP2 poses a risk of severe neurological complications. These challenges have significantly impeded the progress of gene supplementation therapies. Consequently, the focus has shifted towards DNA/RNA editing approaches aimed at correcting MECP2 mutations and restoring physiological levels of MECP2 protein expression. Notably, several research groups have successfully employed CRISPR-based gene editing technologies to rectify MECP2 mutations in induced pluripotent stem cells (iPSCs) or patient-derived cells ex vivo [1-2]. Given the pivotal role of animal models in preclinical research, the development of humanized mouse models expressing the human MECP2 gene is crucial. These models facilitate the transition of gene therapy candidates—encompassing small nucleic acids, CRISPR-based editors, base editors, and RNA editing technologies—into clinical stages [3-4].
This strain is a humanized MECP2 gene mouse model, generated by replacing the endogenous mouse Mecp2 gene with the human MECP2 gene harboring the T158M mutation through embryonic stem cell targeting techniques. This mutation represents the most common human RTT-associated missense mutation in MECP2. Studies have shown that mice carrying this mutation recapitulate many clinical features of RTT [5].
Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder primarily affecting female infants and young children, with an incidence of approximately 1 in 10,000 to 15,000 females. Characteristic clinical features include intellectual disability, loss of language skills, stereotypic hand movements, and gait disturbances. Affected individuals typically experience a period of normal development, followed by deceleration in head circumference growth between 6 to 18 months of age, and subsequent regression of acquired motor and cognitive abilities. Overt impairments in cognition and motor function generally emerge within 1 to 2 years. Mutations in the methyl-CpG-binding protein 2 (MECP2) gene are responsible for over 90% of RTT cases. MECP2 is a nuclear protein that binds methylated DNA to modulate gene transcription. MECP2 gene duplications lead to MECP2 duplication syndrome (MDS), while MECP2 deficiency disrupts central nervous system maturation, adversely affecting learning and memory, culminating in the clinical manifestations of RTT.
Current therapeutic strategies for RTT primarily revolve around gene supplementation using adeno-associated virus (AAV) vectors to deliver functional human MECP2 genes to compensate for the endogenous deficiency. However, the substantial size of the MECP2 gene surpasses the packaging capacity of most viral vectors, and overexpression of MECP2 poses a risk of severe neurological complications. These challenges have significantly impeded the progress of gene supplementation therapies. Consequently, the focus has shifted towards DNA/RNA editing approaches aimed at correcting MECP2 mutations and restoring physiological levels of MECP2 protein expression. Notably, several research groups have successfully employed CRISPR-based gene editing technologies to rectify MECP2 mutations in induced pluripotent stem cells (iPSCs) or patient-derived cells ex vivo [1-2]. Given the pivotal role of animal models in preclinical research, the development of humanized mouse models expressing the human MECP2 gene is crucial. These models facilitate the transition of gene therapy candidates—encompassing small nucleic acids, CRISPR-based editors, base editors, and RNA editing technologies—into clinical stages [3-4].
This strain is a humanized MECP2 gene mouse model, generated by replacing the endogenous mouse Mecp2 gene with the human MECP2 gene harboring the T158M mutation through embryonic stem cell targeting techniques. This mutation represents the most common human RTT-associated missense mutation in MECP2. Studies have shown that mice carrying this mutation recapitulate many clinical features of RTT [5].
B6-hATP7B*H1069Q
Product ID:
C001610
Strain:
C57BL/6NCya
Status:
Description:
Hepatolenticular degeneration (HLD), also known as Wilson disease (WD), is an autosomal recessive copper transport disorder that can lead to liver failure. The incidence rate is about 1:30,000 [1]. The clinical manifestations of HLD mainly include chronic liver damage, and neurological and psychiatric symptoms, and can occasionally cause acute liver failure and hemolytic anemia. Its typical manifestation is the combination of liver disease and movement disorders in adolescence or early adulthood, but there is a large variation in phenotypic differences among patients, and up to 60% of patients have neurological or psychiatric symptoms [2]. Studies have shown that mutations in the ATP7B gene are associated with HLD. The characteristic feature is that with the loss of functional ATP7B protein, the clearance of excess copper is affected, leading to copper accumulation to toxic levels, damaging tissues and organs such as the liver and brain [1, 3-4]. The copper ion transport ATPase β-peptide encoded by the ATP7B gene is a member of the P-type cation transport ATPase family. This family uses the energy stored in ATP to transport metals into and out of cells. The ATP7B protein consists of multiple transmembrane domains, an ATPase consensus sequence, a hinge domain, a phosphorylation site, and at least two putative copper-binding sites [5]. This protein mainly exists in the liver, with small amounts found in the kidneys and brain. Its function as a copper transport ATPase plays a role in transporting copper from the liver to other parts of the body. More than 900 pathogenic mutations of the ATP7B gene have been reported, with the mutation types mainly concentrated in missense, nonsense, or frameshift mutations, and other mechanisms include exon skipping, large deletions, and intron variations. The most common mutation in patients from Northern and Eastern Europe is H1069Q, but its frequency varies greatly among countries [2].
Hepatolenticular degeneration (HLD) treatments are mainly categorized into pharmacotherapy and surgical intervention. Pharmacotherapy is aimed at alleviating symptoms, preventing disease progression, and preventing complications, while surgery is typically liver transplantation. With the continuous exploration of the genetic etiology of Wilson’s disease, targeted gene therapy is expected to become the next "star therapy." Currently, multiple biotechnology companies and research institutions, including Prime Medicine and LogicBio Therapeutics, are developing a variety of gene editing therapies based on CRISPR/Cas9, Prime Editor, or other technologies to correct mutations in the ATP7B gene or replace the mutated ATP7B gene as a whole. These highly promising therapies are currently in preclinical studies [6-15]. Given that these gene editing therapies require precise targeting of the human ATP7B gene, humanizing mouse genes will help accelerate the entry of gene therapy into the clinical stage. This strain is a humanized point mutation model constructed by introducing the common pathogenic mutation p.H1069Q (CAC>CAA) into the humanized ATP7B gene of B6-hATP7B mice (Catalog No.: I001130). This model is suitable for studying the pathogenic mechanisms of Wilson's disease, and homozygous animals 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 to meet the experimental needs.
Hepatolenticular degeneration (HLD), also known as Wilson disease (WD), is an autosomal recessive copper transport disorder that can lead to liver failure. The incidence rate is about 1:30,000 [1]. The clinical manifestations of HLD mainly include chronic liver damage, and neurological and psychiatric symptoms, and can occasionally cause acute liver failure and hemolytic anemia. Its typical manifestation is the combination of liver disease and movement disorders in adolescence or early adulthood, but there is a large variation in phenotypic differences among patients, and up to 60% of patients have neurological or psychiatric symptoms [2]. Studies have shown that mutations in the ATP7B gene are associated with HLD. The characteristic feature is that with the loss of functional ATP7B protein, the clearance of excess copper is affected, leading to copper accumulation to toxic levels, damaging tissues and organs such as the liver and brain [1, 3-4]. The copper ion transport ATPase β-peptide encoded by the ATP7B gene is a member of the P-type cation transport ATPase family. This family uses the energy stored in ATP to transport metals into and out of cells. The ATP7B protein consists of multiple transmembrane domains, an ATPase consensus sequence, a hinge domain, a phosphorylation site, and at least two putative copper-binding sites [5]. This protein mainly exists in the liver, with small amounts found in the kidneys and brain. Its function as a copper transport ATPase plays a role in transporting copper from the liver to other parts of the body. More than 900 pathogenic mutations of the ATP7B gene have been reported, with the mutation types mainly concentrated in missense, nonsense, or frameshift mutations, and other mechanisms include exon skipping, large deletions, and intron variations. The most common mutation in patients from Northern and Eastern Europe is H1069Q, but its frequency varies greatly among countries [2].
Hepatolenticular degeneration (HLD) treatments are mainly categorized into pharmacotherapy and surgical intervention. Pharmacotherapy is aimed at alleviating symptoms, preventing disease progression, and preventing complications, while surgery is typically liver transplantation. With the continuous exploration of the genetic etiology of Wilson’s disease, targeted gene therapy is expected to become the next "star therapy." Currently, multiple biotechnology companies and research institutions, including Prime Medicine and LogicBio Therapeutics, are developing a variety of gene editing therapies based on CRISPR/Cas9, Prime Editor, or other technologies to correct mutations in the ATP7B gene or replace the mutated ATP7B gene as a whole. These highly promising therapies are currently in preclinical studies [6-15]. Given that these gene editing therapies require precise targeting of the human ATP7B gene, humanizing mouse genes will help accelerate the entry of gene therapy into the clinical stage. This strain is a humanized point mutation model constructed by introducing the common pathogenic mutation p.H1069Q (CAC>CAA) into the humanized ATP7B gene of B6-hATP7B mice (Catalog No.: I001130). This model is suitable for studying the pathogenic mechanisms of Wilson's disease, and homozygous animals 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 to meet the experimental needs.
B6-hTARDBP
Product ID:
C001418
Strain:
C57BL/6JCya
Status:
Description:
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a fatal progressive neurodegenerative disease characterized by the degeneration and death of motor neurons in the central nervous system. This loss of motor neurons leads to progressive muscle weakness and atrophy, ultimately culminating in the complete loss of voluntary muscle control. Consequently, ALS can induce speech, swallowing, and respiratory difficulties [1]. Critically, unlike Alzheimer's disease, ALS does not necessarily impact higher-order cognitive functions. Remarkably, patients in advanced stages of the disease can maintain clear thinking and retain their premorbid memory, personality, and intelligence. Several genes have been identified as causative factors in ALS, including SOD1, ALS2, TARDBP, and FUS. Among them, TARDBP (TAR DNA-binding protein) is a gene encoding a protein involved in diverse cellular functions, including facilitating nuclear protein import, regulating circadian rhythms, and maintaining protein stability [2]. Mutations in the TARDBP gene are linked to ALS. These mutations can lead to abnormal TDP-43 protein accumulation and its mislocalization to the cytoplasm, a key pathological hallmark of the disease [3].
TARDBP-targeted therapy is mainly based on monoclonal antibody drugs, most of which are still in the preclinical stage of development. Oligonucleotides such as ASO and gene therapy have also been reported in the literature. These drugs are mainly used for the treatment of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TARDBP is a new and popular target for the treatment of ALS. Preclinical disease research models are mainly transgenic (TG) or point mutation (PM) mice. To advance TARDBP-targeted drug therapies, especially gene and oligonucleotide therapies, Cyagen has independently developed a mouse Tardbp gene humanized model, which replaces the mouse Tardbp gene with the human TARDBP gene through gene editing technology. It can be used to study neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal dementia. The homozygous B6-hTARDBP mice are viable and fertile. In addition, based on the technological innovation of TurboKnockout fusion BAC recombination, Cyagen can also provide popular point mutation disease models based on this model and can provide customized services according to different point mutations to meet the needs of researchers for amyotrophic lateral sclerosis and frontotemporal dementia.
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a fatal progressive neurodegenerative disease characterized by the degeneration and death of motor neurons in the central nervous system. This loss of motor neurons leads to progressive muscle weakness and atrophy, ultimately culminating in the complete loss of voluntary muscle control. Consequently, ALS can induce speech, swallowing, and respiratory difficulties [1]. Critically, unlike Alzheimer's disease, ALS does not necessarily impact higher-order cognitive functions. Remarkably, patients in advanced stages of the disease can maintain clear thinking and retain their premorbid memory, personality, and intelligence. Several genes have been identified as causative factors in ALS, including SOD1, ALS2, TARDBP, and FUS. Among them, TARDBP (TAR DNA-binding protein) is a gene encoding a protein involved in diverse cellular functions, including facilitating nuclear protein import, regulating circadian rhythms, and maintaining protein stability [2]. Mutations in the TARDBP gene are linked to ALS. These mutations can lead to abnormal TDP-43 protein accumulation and its mislocalization to the cytoplasm, a key pathological hallmark of the disease [3].
TARDBP-targeted therapy is mainly based on monoclonal antibody drugs, most of which are still in the preclinical stage of development. Oligonucleotides such as ASO and gene therapy have also been reported in the literature. These drugs are mainly used for the treatment of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TARDBP is a new and popular target for the treatment of ALS. Preclinical disease research models are mainly transgenic (TG) or point mutation (PM) mice. To advance TARDBP-targeted drug therapies, especially gene and oligonucleotide therapies, Cyagen has independently developed a mouse Tardbp gene humanized model, which replaces the mouse Tardbp gene with the human TARDBP gene through gene editing technology. It can be used to study neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal dementia. The homozygous B6-hTARDBP mice are viable and fertile. In addition, based on the technological innovation of TurboKnockout fusion BAC recombination, Cyagen can also provide popular point mutation disease models based on this model and can provide customized services according to different point mutations to meet the needs of researchers for amyotrophic lateral sclerosis and frontotemporal dementia.
B6-hTGFBI
Product ID:
C001546
Strain:
C57BL/6JCya
Status:
Description:
Corneal dystrophy (CD) refers to a group of primary hereditary progressive corneal diseases. The typical clinical presentation involves gradual loss of corneal transparency in both eyes, often leading to recurrent corneal erosions and visual impairment. The TGFBI gene (also known as BIGH3) encodes an extracellular matrix protein called keratoepithelin (KE protein), which plays a role in cell growth, differentiation, wound healing, cell adhesion, migration, apoptosis, proliferation, and tumorigenesis [1]. Mutations in the TGFBI gene are associated with various types of corneal dystrophy. Abnormal accumulation of mutated TGFBI deposits in the corneal epithelium and stroma progressively affects corneal transparency, leading to visual impairment.
Currently, therapeutic pipelines targeting the TGFBI gene have entered preclinical research stages. For instance, SiSaf Ltd. is developing a siRNA drug pipeline called SIS-201-CD, which aims to treat the disease by specifically inhibiting abnormal TGFBI expression. Most gene therapies target human genes, but considering the genetic differences between animals and humans, humanizing mouse genes can accelerate the development of TGFBI-targeted gene therapies for clinical use. This strain is a mouse Tgfbi gene humanized model and can be used for research on CD. The homozygous B6-hTGFBI 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 related to CD.
Corneal dystrophy (CD) refers to a group of primary hereditary progressive corneal diseases. The typical clinical presentation involves gradual loss of corneal transparency in both eyes, often leading to recurrent corneal erosions and visual impairment. The TGFBI gene (also known as BIGH3) encodes an extracellular matrix protein called keratoepithelin (KE protein), which plays a role in cell growth, differentiation, wound healing, cell adhesion, migration, apoptosis, proliferation, and tumorigenesis [1]. Mutations in the TGFBI gene are associated with various types of corneal dystrophy. Abnormal accumulation of mutated TGFBI deposits in the corneal epithelium and stroma progressively affects corneal transparency, leading to visual impairment.
Currently, therapeutic pipelines targeting the TGFBI gene have entered preclinical research stages. For instance, SiSaf Ltd. is developing a siRNA drug pipeline called SIS-201-CD, which aims to treat the disease by specifically inhibiting abnormal TGFBI expression. Most gene therapies target human genes, but considering the genetic differences between animals and humans, humanizing mouse genes can accelerate the development of TGFBI-targeted gene therapies for clinical use. This strain is a mouse Tgfbi gene humanized model and can be used for research on CD. The homozygous B6-hTGFBI 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 related to CD.
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