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Abcb1a/Abcb1b-DKO(FVB)
Product ID:
C001493
Strain:
FVB/NJCya
Status:
Description:
P-glycoprotein (P-gp), also known as multidrug resistance protein 1 (MDR1), is an ATP-binding cassette transporter that acts as a biological barrier by expelling toxins and foreign substances from cells. P-gp is capable of transporting many structurally and functionally different compounds out of cells [1]. However, the mechanism of MDR1 also prevents the uptake of many cancer treatment drugs by cells, leading to multidrug resistance (MDR) [2]. In normal organisms, MDR1’s distribution in the blood-brain barrier and blood-placenta barrier prevents exogenous drugs and toxins from entering the central nervous system and placenta of the organism, thereby protecting the organism and enabling it to perform normal physiological functions. In pathological conditions, however, the MDR1 in the blood-brain barrier prevents drugs from entering the central nervous system, and in tumor cells, leads to the development of MDR. The evolution of MDR remains one of the major obstacles to controlling or curing cancer [3-4].
In humans, the MDR1 protein is encoded by the ABCB1 gene. In mice, two closely located genes, Abcb1a and Abcb1b, encode the MDR1a and MDR1b subtypes of this protein. Mouse MDR1a and MDR1b have 80% homology with human MDR1. MDR1a and MDR1b have the same function as human MDR1 protein in resisting anticancer drugs. Although mouse MDR1a and MDR1b proteins are distributed in different tissues of the body, their overall distribution is consistent with that of human MDR1 protein [5-6]. In summary, the distribution and function of mouse MDR1a and MDR1b are consistent with those of human MDR1.
This strain is an MDR1 knockout model, in which the human ABCB1 gene’s homologous genes, Abcb1a and Abcb1b, were knocked out in mice using gene editing technology. This model lacks the expression of MDR1 protein and can be used for research in areas such as blood-brain barrier permeability-related diseases and multidrug resistance of anti-tumor drugs.
P-glycoprotein (P-gp), also known as multidrug resistance protein 1 (MDR1), is an ATP-binding cassette transporter that acts as a biological barrier by expelling toxins and foreign substances from cells. P-gp is capable of transporting many structurally and functionally different compounds out of cells [1]. However, the mechanism of MDR1 also prevents the uptake of many cancer treatment drugs by cells, leading to multidrug resistance (MDR) [2]. In normal organisms, MDR1’s distribution in the blood-brain barrier and blood-placenta barrier prevents exogenous drugs and toxins from entering the central nervous system and placenta of the organism, thereby protecting the organism and enabling it to perform normal physiological functions. In pathological conditions, however, the MDR1 in the blood-brain barrier prevents drugs from entering the central nervous system, and in tumor cells, leads to the development of MDR. The evolution of MDR remains one of the major obstacles to controlling or curing cancer [3-4].
In humans, the MDR1 protein is encoded by the ABCB1 gene. In mice, two closely located genes, Abcb1a and Abcb1b, encode the MDR1a and MDR1b subtypes of this protein. Mouse MDR1a and MDR1b have 80% homology with human MDR1. MDR1a and MDR1b have the same function as human MDR1 protein in resisting anticancer drugs. Although mouse MDR1a and MDR1b proteins are distributed in different tissues of the body, their overall distribution is consistent with that of human MDR1 protein [5-6]. In summary, the distribution and function of mouse MDR1a and MDR1b are consistent with those of human MDR1.
This strain is an MDR1 knockout model, in which the human ABCB1 gene’s homologous genes, Abcb1a and Abcb1b, were knocked out in mice using gene editing technology. This model lacks the expression of MDR1 protein and can be used for research in areas such as blood-brain barrier permeability-related diseases and multidrug resistance of anti-tumor drugs.
BALB/c;B6J-Rosa26-hHRAS
Product ID:
I001214
Strain:
BALB/c;B6JCya
Status:
Description:
The HRas oncogene (HRAS), also known as the Harvey Rat Sarcoma Viral Oncogene Homolog (HRAS), is a member of the Ras oncogene family, which also includes KRAS and NRAS. All members of this family are associated with the development of mammalian sarcoma retroviruses [1]. HRAS encodes the H-Ras protein, a small GTPase responsible for transmitting signals from cell surface receptors to the nucleus, regulating cell proliferation, survival, and differentiation. HRAS is primarily expressed in various tissues, including the brain, heart, and skeletal muscle, and is involved in controlling the cellular response to growth factors. As a member of the small GTPase family, HRAS acts as a molecular switch, cycling between active and inactive states to influence key cellular processes. Mutations in the HRAS gene can lead to abnormal signal transduction, commonly found in tumors of stratified epithelial tissues, such as bladder cancer, thyroid cancer, and head and neck squamous cell carcinoma. Additionally, HRAS is associated with Costello syndrome, a genetic disorder characterized by developmental delays and an increased risk of tumors [2-3].
Early studies have shown that genotoxic carcinogens shorten the latency period and increase the incidence of malignant tumors in rasH2 mice, which carry the human HRAS (c-Ha-ras) oncogene, compared to non-transgenic mice. Therefore, rasH2 mice are ideal animal models for rapid carcinogenicity testing [4-5]. Further research has shown that F1 hybrid mice (CB6F1 background rasH2 mice) obtained by mating male C57BL/6J mice carrying the human prototype c-Ha-ras gene with female BALB/c mice are significantly more sensitive to both mutagenic and non-mutagenic carcinogens than control mice [5]. These mice are highly sensitive to the carcinogenicity of both genotoxic and non-genotoxic compounds while showing no response to non-carcinogens [6]. Between 12 to 18 months of age, rasH2 mice primarily develop spontaneous alveolar adenomas/bronchial adenomas/adenocarcinomas, splenic hemangiomas/hemangiosarcomas, and a smaller number of skin and gastric papillomas and lymphomas [4]. In the 1990s, this mouse model was officially approved by the FDA for carcinogenicity evaluations in drug safety assessments, reducing the standard two-year carcinogenicity test in common rodents to six months.
BALB/c;B6J-Rosa26-hHRAS mice are obtained by crossing Rosa26-hHRAS mice on a C57BL/6JCya background (Catalog No.: I001213) with BALB/cAnCya mice. This hybrid strain exhibits higher sensitivity to both genotoxic and non-genotoxic human carcinogens. BALB/c;B6J-Rosa26-hHRAS mice can be used for rapid in vivo testing of the carcinogenicity of genotoxic and non-genotoxic compounds, studying the impact of HRAS oncogene point mutations on tumorigenesis and development, and developing tumor prevention or suppression therapies.
The HRas oncogene (HRAS), also known as the Harvey Rat Sarcoma Viral Oncogene Homolog (HRAS), is a member of the Ras oncogene family, which also includes KRAS and NRAS. All members of this family are associated with the development of mammalian sarcoma retroviruses [1]. HRAS encodes the H-Ras protein, a small GTPase responsible for transmitting signals from cell surface receptors to the nucleus, regulating cell proliferation, survival, and differentiation. HRAS is primarily expressed in various tissues, including the brain, heart, and skeletal muscle, and is involved in controlling the cellular response to growth factors. As a member of the small GTPase family, HRAS acts as a molecular switch, cycling between active and inactive states to influence key cellular processes. Mutations in the HRAS gene can lead to abnormal signal transduction, commonly found in tumors of stratified epithelial tissues, such as bladder cancer, thyroid cancer, and head and neck squamous cell carcinoma. Additionally, HRAS is associated with Costello syndrome, a genetic disorder characterized by developmental delays and an increased risk of tumors [2-3].
Early studies have shown that genotoxic carcinogens shorten the latency period and increase the incidence of malignant tumors in rasH2 mice, which carry the human HRAS (c-Ha-ras) oncogene, compared to non-transgenic mice. Therefore, rasH2 mice are ideal animal models for rapid carcinogenicity testing [4-5]. Further research has shown that F1 hybrid mice (CB6F1 background rasH2 mice) obtained by mating male C57BL/6J mice carrying the human prototype c-Ha-ras gene with female BALB/c mice are significantly more sensitive to both mutagenic and non-mutagenic carcinogens than control mice [5]. These mice are highly sensitive to the carcinogenicity of both genotoxic and non-genotoxic compounds while showing no response to non-carcinogens [6]. Between 12 to 18 months of age, rasH2 mice primarily develop spontaneous alveolar adenomas/bronchial adenomas/adenocarcinomas, splenic hemangiomas/hemangiosarcomas, and a smaller number of skin and gastric papillomas and lymphomas [4]. In the 1990s, this mouse model was officially approved by the FDA for carcinogenicity evaluations in drug safety assessments, reducing the standard two-year carcinogenicity test in common rodents to six months.
BALB/c;B6J-Rosa26-hHRAS mice are obtained by crossing Rosa26-hHRAS mice on a C57BL/6JCya background (Catalog No.: I001213) with BALB/cAnCya mice. This hybrid strain exhibits higher sensitivity to both genotoxic and non-genotoxic human carcinogens. BALB/c;B6J-Rosa26-hHRAS mice can be used for rapid in vivo testing of the carcinogenicity of genotoxic and non-genotoxic compounds, studying the impact of HRAS oncogene point mutations on tumorigenesis and development, and developing tumor prevention or suppression therapies.
B6-H11-hBDCA2 (hCLEC4C)
Product ID:
C001693
Strain:
C57BL/6NCya
Status:
Description:
The CLEC4C gene, also known as BDCA-2 or CD303, encodes a type II transmembrane C-type lectin receptor predominantly expressed by plasmacytoid dendritic cells (pDCs) [1]. This receptor plays a critical role in pDC biology and serves as a key marker for this cell type [2]. The CLEC4C protein, featuring a carbohydrate recognition domain, is implicated in the capture and subsequent processing of antigens, potentially through the recognition of specific glycans and immunoglobulin G [1]. Functionally, CLEC4C acts as a signaling receptor within pDCs, and its engagement can negatively regulate the production of type I interferons, thereby modulating immune responses [2]. Notably, dysregulation of CLEC4C expression and pDC function has been associated with the pathogenesis of autoimmune disorders, including systemic lupus erythematosus (SLE), as well as in the context of certain hematological malignancies [3]. Litifilimab is a monoclonal antibody that targets CLEC4C and is under investigation for the treatment of SLE and other interferonopathies [4].
B6-H11-hCLEC4C mice are humanized models generated by gene editing technology, in which the human CLEC4C genomic DNA was inserted at the H11 safe harbor. This modification does not affect the expression of the mouse homologous gene Clec4b1. This model can be used to study the pathological mechanisms and therapeutic methods of autoimmune disorders and hematological malignancies, as well as the screening and development of CLEC4C-targeted drugs, and preclinical efficacy and safety evaluations.
The CLEC4C gene, also known as BDCA-2 or CD303, encodes a type II transmembrane C-type lectin receptor predominantly expressed by plasmacytoid dendritic cells (pDCs) [1]. This receptor plays a critical role in pDC biology and serves as a key marker for this cell type [2]. The CLEC4C protein, featuring a carbohydrate recognition domain, is implicated in the capture and subsequent processing of antigens, potentially through the recognition of specific glycans and immunoglobulin G [1]. Functionally, CLEC4C acts as a signaling receptor within pDCs, and its engagement can negatively regulate the production of type I interferons, thereby modulating immune responses [2]. Notably, dysregulation of CLEC4C expression and pDC function has been associated with the pathogenesis of autoimmune disorders, including systemic lupus erythematosus (SLE), as well as in the context of certain hematological malignancies [3]. Litifilimab is a monoclonal antibody that targets CLEC4C and is under investigation for the treatment of SLE and other interferonopathies [4].
B6-H11-hCLEC4C mice are humanized models generated by gene editing technology, in which the human CLEC4C genomic DNA was inserted at the H11 safe harbor. This modification does not affect the expression of the mouse homologous gene Clec4b1. This model can be used to study the pathological mechanisms and therapeutic methods of autoimmune disorders and hematological malignancies, as well as the screening and development of CLEC4C-targeted drugs, and preclinical efficacy and safety evaluations.
B6-hTTN
Product ID:
C001819
Strain:
C57BL/6NCya
Status:
Description:
The TTN gene provides instructions for making titin, the largest known protein in the human body, essential for the structure, flexibility, and stability of sarcomeres, the fundamental contractile units of muscle [1]. Titin is primarily expressed in striated muscle, including skeletal muscle and cardiac muscle, where it acts as a molecular spring and scaffold, interacting with other muscle proteins like actin and myosin to maintain sarcomere integrity during muscle contraction and relaxation [2]. The TTN gene undergoes extensive alternative splicing, leading to the production of various titin isoforms with differing elastic properties, which contributes to the diverse mechanical characteristics of different muscle types. Mutations in TTN are a leading cause of various muscle and heart disorders, collectively known as titinopathies. These include familial dilated cardiomyopathy (DCM), a common cause of heart failure characterized by weakening and enlargement of the heart, often due to truncating variants in TTN. Other associated conditions include early-onset myopathy with fatal cardiomyopathy, centronuclear myopathy, limb-girdle muscular dystrophy, and tibial muscular dystrophy [3].
The B6-hTTN mouse is a humanized model constructed via gene-editing technology. The sequence from the ATG start codon to the TAA stop codon of mouse Ttn will be replaced with the sequence from the ATG start codon to the TAA stop codon of human TTN. B6-hTTN mice can be used to study the pathogenesis of hereditary muscle diseases such as familial dilated cardiomyopathy (DCM), early-onset myopathy, and muscular dystrophy, as well as for the screening, development, and safety evaluation of TTN-targeted drugs.
The TTN gene provides instructions for making titin, the largest known protein in the human body, essential for the structure, flexibility, and stability of sarcomeres, the fundamental contractile units of muscle [1]. Titin is primarily expressed in striated muscle, including skeletal muscle and cardiac muscle, where it acts as a molecular spring and scaffold, interacting with other muscle proteins like actin and myosin to maintain sarcomere integrity during muscle contraction and relaxation [2]. The TTN gene undergoes extensive alternative splicing, leading to the production of various titin isoforms with differing elastic properties, which contributes to the diverse mechanical characteristics of different muscle types. Mutations in TTN are a leading cause of various muscle and heart disorders, collectively known as titinopathies. These include familial dilated cardiomyopathy (DCM), a common cause of heart failure characterized by weakening and enlargement of the heart, often due to truncating variants in TTN. Other associated conditions include early-onset myopathy with fatal cardiomyopathy, centronuclear myopathy, limb-girdle muscular dystrophy, and tibial muscular dystrophy [3].
The B6-hTTN mouse is a humanized model constructed via gene-editing technology. The sequence from the ATG start codon to the TAA stop codon of mouse Ttn will be replaced with the sequence from the ATG start codon to the TAA stop codon of human TTN. B6-hTTN mice can be used to study the pathogenesis of hereditary muscle diseases such as familial dilated cardiomyopathy (DCM), early-onset myopathy, and muscular dystrophy, as well as for the screening, development, and safety evaluation of TTN-targeted drugs.
B6-F8 KO
Product ID:
I001219
Strain:
C57BL/6JCya
Status:
Description:
The F8 gene encodes coagulation factor VIII (FVIII), a large plasma glycoprotein crucial for the intrinsic pathway of blood coagulation. This gene generates two alternatively spliced transcripts, with the larger isoform, variant a, forming a non-covalent complex with von Willebrand factor (vWF) that circulates in plasma. Under normal physiological conditions, when a blood vessel is injured, platelets and clotting factors aggregate at the site of injury to form a blood clot and prevent further bleeding. In this process, FVIII functions as a cofactor, working synergistically with activated factor IX (FIXa) to activate factor X (FX), subsequently generating fibrin and stabilizing the blood clot. Deficiency of the F8 gene leads to hemophilia A (HA), an X-linked recessive bleeding disorder that primarily affects males. Patients often present with spontaneous or post-traumatic bleeding that may be difficult to control, with severe cases risking disability or life-threatening complications due to internal bleeding and joint hemorrhage. Clinically, exogenous FVIII supplementation is effective in managing hemophilia A symptoms. In recent years, advances in gene therapy and gene editing have offered new hope for HA treatment, aiming for a long-term or permanent cure by repairing or replacing the defective F8 gene.
The B6-F8 KO mouse is a hemophilia A (HA) research model developed through gene-editing techniques, where the murine F8 gene, homologous to the human F8 gene, is knocked out. Studies have shown that homozygous F8 knockout mice are viable and develop normally [1]. Since the murine F8 gene is located on the X chromosome, hemizygous male and homozygous female B6-F8 KO mice exhibit a consistent phenotype with significantly lower FVIII activity compared to wild-type mice, prolonged clotting time, and a classic hemophilia A phenotype [1].
The F8 gene encodes coagulation factor VIII (FVIII), a large plasma glycoprotein crucial for the intrinsic pathway of blood coagulation. This gene generates two alternatively spliced transcripts, with the larger isoform, variant a, forming a non-covalent complex with von Willebrand factor (vWF) that circulates in plasma. Under normal physiological conditions, when a blood vessel is injured, platelets and clotting factors aggregate at the site of injury to form a blood clot and prevent further bleeding. In this process, FVIII functions as a cofactor, working synergistically with activated factor IX (FIXa) to activate factor X (FX), subsequently generating fibrin and stabilizing the blood clot. Deficiency of the F8 gene leads to hemophilia A (HA), an X-linked recessive bleeding disorder that primarily affects males. Patients often present with spontaneous or post-traumatic bleeding that may be difficult to control, with severe cases risking disability or life-threatening complications due to internal bleeding and joint hemorrhage. Clinically, exogenous FVIII supplementation is effective in managing hemophilia A symptoms. In recent years, advances in gene therapy and gene editing have offered new hope for HA treatment, aiming for a long-term or permanent cure by repairing or replacing the defective F8 gene.
The B6-F8 KO mouse is a hemophilia A (HA) research model developed through gene-editing techniques, where the murine F8 gene, homologous to the human F8 gene, is knocked out. Studies have shown that homozygous F8 knockout mice are viable and develop normally [1]. Since the murine F8 gene is located on the X chromosome, hemizygous male and homozygous female B6-F8 KO mice exhibit a consistent phenotype with significantly lower FVIII activity compared to wild-type mice, prolonged clotting time, and a classic hemophilia A phenotype [1].
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.
Col7a1-KO
Product ID:
C001539
Strain:
C57BL/6JCya
Status:
Description:
Epidermolysis Bullosa (EB) is a genetic skin disease characterized by the formation of blisters and bullae on the skin and mucous membranes following minor trauma or friction. Common clinical symptoms include the appearance of blisters, blood blisters, and erosion on the skin. Depending on the site of onset, hereditary EB can be divided into three types: Simplex Epidermolysis Bullosa (EBS), Junctional Epidermolysis Bullosa (JEB), and Dystrophic Epidermolysis Bullosa (DEB). Mutations in the COL7A1 gene are the cause of Dystrophic Epidermolysis Bullosa (DEB), and the different clinical phenotypes presented by DEB are related to the mutation site and form of the COL7A1 gene. The COL7A1 gene encodes type VII collagen protein, which forms anchoring fibrils that bind the dermal tissue to the epidermal tissue. Functional deficiency of anchoring fibrils caused by COL7A1 mutations makes the patient's skin extremely fragile, easily causing blisters or tears due to minor friction or trauma. To date, at least 324 pathogenic mutations related to DEB have been found in the COL7A1 gene, including nonsense, missense, deletion, insertion, splicing, and regulatory mutations [1]. Research shows that Col7a1 gene homozygous knockout mice exhibit high mortality after birth, with hemorrhagic blisters appearing on the palms of the forepaws and hind paws within 24-48 hours, followed by severe RDEB symptoms [2]. This is one of the commonly used preclinical models for DEB research.
Col7a1-KO mice, constructed by using gene editing technology to knock out the homologous gene Col7a1 of human COL7A1 in mice, serve as a research model for Dystrophic Epidermolysis Bullosa (DEB). Homozygous Col7a1-KO mice lack the expression of the Col7a1 gene and COL7A1 protein, and exhibit symptoms of skin redness and blistering on the palms of the fore and hind paws on the first day after birth, and die within three days after birth. Histological examination results show that the skin of Col7a1-KO mice exhibits significant subcutaneous edema, and there is a separation between the epidermis and dermis, which is roughly the same as the pathogenesis and pathological characteristics of human Dystrophic Epidermolysis Bullosa (DEB) in the clinic. Therefore, Col7a1-KO mice can be used for the mechanistic study of Dystrophic Epidermolysis Bullosa (DEB), as well as the development, screening, and evaluation of therapeutic drugs.
Epidermolysis Bullosa (EB) is a genetic skin disease characterized by the formation of blisters and bullae on the skin and mucous membranes following minor trauma or friction. Common clinical symptoms include the appearance of blisters, blood blisters, and erosion on the skin. Depending on the site of onset, hereditary EB can be divided into three types: Simplex Epidermolysis Bullosa (EBS), Junctional Epidermolysis Bullosa (JEB), and Dystrophic Epidermolysis Bullosa (DEB). Mutations in the COL7A1 gene are the cause of Dystrophic Epidermolysis Bullosa (DEB), and the different clinical phenotypes presented by DEB are related to the mutation site and form of the COL7A1 gene. The COL7A1 gene encodes type VII collagen protein, which forms anchoring fibrils that bind the dermal tissue to the epidermal tissue. Functional deficiency of anchoring fibrils caused by COL7A1 mutations makes the patient's skin extremely fragile, easily causing blisters or tears due to minor friction or trauma. To date, at least 324 pathogenic mutations related to DEB have been found in the COL7A1 gene, including nonsense, missense, deletion, insertion, splicing, and regulatory mutations [1]. Research shows that Col7a1 gene homozygous knockout mice exhibit high mortality after birth, with hemorrhagic blisters appearing on the palms of the forepaws and hind paws within 24-48 hours, followed by severe RDEB symptoms [2]. This is one of the commonly used preclinical models for DEB research.
Col7a1-KO mice, constructed by using gene editing technology to knock out the homologous gene Col7a1 of human COL7A1 in mice, serve as a research model for Dystrophic Epidermolysis Bullosa (DEB). Homozygous Col7a1-KO mice lack the expression of the Col7a1 gene and COL7A1 protein, and exhibit symptoms of skin redness and blistering on the palms of the fore and hind paws on the first day after birth, and die within three days after birth. Histological examination results show that the skin of Col7a1-KO mice exhibits significant subcutaneous edema, and there is a separation between the epidermis and dermis, which is roughly the same as the pathogenesis and pathological characteristics of human Dystrophic Epidermolysis Bullosa (DEB) in the clinic. Therefore, Col7a1-KO mice can be used for the mechanistic study of Dystrophic Epidermolysis Bullosa (DEB), as well as the development, screening, and evaluation of therapeutic drugs.
CB17-SCID-Ces1c-KO
Product ID:
C001972
Strain:
C.B-17
Status:
Description:
Ces1c, the mouse carboxylesterase 1C (Carboxylesterase 1C) gene, encodes an enzyme highly expressed in rodent plasma, responsible for hydrolyzing various ester- or amide-containing drugs, particularly cleavable linkers (Linker) in antibody-drug conjugates (ADCs) such as Val-Cit (VC) linkers [1-2]. Mouse Ces1c causes non-specific hydrolysis of ADCs in plasma, accelerating drug clearance and severely deviating pharmacokinetic (PK) profiles from human reality [3-4]. In humans, CES1 and CES2 are mainly distributed in the liver and intestine, with negligible activity in plasma, whereas mouse Ces1c, lacking an endoplasmic reticulum retention signal, is secreted in large amounts into plasma [3-4]. Besides its role in drug metabolism, Ces1c is also involved in physiological processes such as lipid metabolism. Studies show that, in evaluating VC-based ADCs, Ces1c in mouse plasma miscleaves the VC-PABC structure, causing premature release of toxic payloads, resulting in systemic toxicity and underestimation of antitumor activity [5-9].
In preclinical evaluation of ADCs, differences in immunodeficient strain backgrounds affect the biodistribution, clearance rates, and reliability of PK/PD results for humanized antibodies [10-15]. For example, highly immunodeficient NOD-SCID and its derivative strains, due to enhanced Fc-FcγR interactions, lead to shortened serum half-life of ADCs and increased off-target organ trapping, thereby underestimating antitumor activity [10-15]. In contrast, the CB17-SCID background exhibits superior characteristics in maintaining antibody half-life and optimizing biodistribution, providing more reliable efficacy data [13-15].
The CB17-SCID-Ces1c-KO mouse is a gene knockout (KO) model, generated on the CB17-SCID immunodeficient background with excellent PK/PD properties, using gene editing technology to knock out the Ces1c gene in mice. This model can be used for ADC drug development, particularly for evaluating VC linker drugs, and to avoid non-specific interference in mouse plasma, provides more clinically predictive efficacy data.
Ces1c, the mouse carboxylesterase 1C (Carboxylesterase 1C) gene, encodes an enzyme highly expressed in rodent plasma, responsible for hydrolyzing various ester- or amide-containing drugs, particularly cleavable linkers (Linker) in antibody-drug conjugates (ADCs) such as Val-Cit (VC) linkers [1-2]. Mouse Ces1c causes non-specific hydrolysis of ADCs in plasma, accelerating drug clearance and severely deviating pharmacokinetic (PK) profiles from human reality [3-4]. In humans, CES1 and CES2 are mainly distributed in the liver and intestine, with negligible activity in plasma, whereas mouse Ces1c, lacking an endoplasmic reticulum retention signal, is secreted in large amounts into plasma [3-4]. Besides its role in drug metabolism, Ces1c is also involved in physiological processes such as lipid metabolism. Studies show that, in evaluating VC-based ADCs, Ces1c in mouse plasma miscleaves the VC-PABC structure, causing premature release of toxic payloads, resulting in systemic toxicity and underestimation of antitumor activity [5-9].
In preclinical evaluation of ADCs, differences in immunodeficient strain backgrounds affect the biodistribution, clearance rates, and reliability of PK/PD results for humanized antibodies [10-15]. For example, highly immunodeficient NOD-SCID and its derivative strains, due to enhanced Fc-FcγR interactions, lead to shortened serum half-life of ADCs and increased off-target organ trapping, thereby underestimating antitumor activity [10-15]. In contrast, the CB17-SCID background exhibits superior characteristics in maintaining antibody half-life and optimizing biodistribution, providing more reliable efficacy data [13-15].
The CB17-SCID-Ces1c-KO mouse is a gene knockout (KO) model, generated on the CB17-SCID immunodeficient background with excellent PK/PD properties, using gene editing technology to knock out the Ces1c gene in mice. This model can be used for ADC drug development, particularly for evaluating VC linker drugs, and to avoid non-specific interference in mouse plasma, provides more clinically predictive efficacy data.
Cftr-KO
Product ID:
C001890
Strain:
C57BL/6JCya
Status:
Description:
Cystic Fibrosis (CF) is an autosomal recessive disorder causing severe damage to the lungs, digestive system, and other organs. It thickens mucus, sweat, and digestive fluids, blocking ducts and channels. The disease manifests as a persistent cough, hyperinflation of lung lobes, chronic nasal congestion, headaches, sleep disorders, digestive and reproductive system disorders, and nutritional and growth development disorders. CF is caused by mutations in the CF-transmembrane conductance regulator (CFTR) gene, which encodes a cAMP-dependent chloride ion channel protein. Abnormal CFTR function can cause transmembrane transport disorders of chloride ions and bicarbonate, leading to mucus obstruction in exocrine glands, and affecting respiration, digestion, endocrine, and reproduction [1-2].
Cftr-KO mice are a gene-knockout (KO) model. Using gene-editing technology, exons 5-6 of the Cftr gene in mice have been knocked out. This model can be used for research on the pathogenic mechanism of cystic fibrosis and the development of related treatment methods. Homozygous Cftr-KO mice start to die at 2 weeks of age, and prophylactic PEG treatment can improve their survival rate [3]. This strain requires feeding with intestinal cleansers to maintain survival after 3 weeks of age.
Cystic Fibrosis (CF) is an autosomal recessive disorder causing severe damage to the lungs, digestive system, and other organs. It thickens mucus, sweat, and digestive fluids, blocking ducts and channels. The disease manifests as a persistent cough, hyperinflation of lung lobes, chronic nasal congestion, headaches, sleep disorders, digestive and reproductive system disorders, and nutritional and growth development disorders. CF is caused by mutations in the CF-transmembrane conductance regulator (CFTR) gene, which encodes a cAMP-dependent chloride ion channel protein. Abnormal CFTR function can cause transmembrane transport disorders of chloride ions and bicarbonate, leading to mucus obstruction in exocrine glands, and affecting respiration, digestion, endocrine, and reproduction [1-2].
Cftr-KO mice are a gene-knockout (KO) model. Using gene-editing technology, exons 5-6 of the Cftr gene in mice have been knocked out. This model can be used for research on the pathogenic mechanism of cystic fibrosis and the development of related treatment methods. Homozygous Cftr-KO mice start to die at 2 weeks of age, and prophylactic PEG treatment can improve their survival rate [3]. This strain requires feeding with intestinal cleansers to maintain survival after 3 weeks of age.
F9-KO
Product ID:
C001509
Strain:
C57BL/6JCya
Status:
Description:
Hemophilia is a group of genetic bleeding disorders that affect the blood’s ability to clot. The common feature of this disease is the generation of abnormal clotting factors, which leads to prolonged clotting time and increased risk of bleeding after minor injuries. In severe cases, spontaneous bleeding can occur even without obvious trauma. As an X-linked recessive disorder, Hemophilia B is more common in males, with approximately 1 in every 30,000 newborn males worldwide being affected [1]. Hemophilia B is caused by mutations in the F9 (FIX) gene, which leads to a deficiency of clotting factor IX. The severity of the disease is usually correlated with the activity level of factor IX in the blood plasma. Mild patients (IX factor activity >5%, >0.05 IU/mL) do not experience spontaneous bleeding, but the amount of bleeding after injury or surgery may increase. Moderate patients (IX factor activity 1%-5%, 0.01-0.05 IU/mL) rarely experience spontaneous bleeding, but even minor injuries can cause prolonged bleeding. Severe patients (IX factor activity <1%, <0.01 IU/mL) experience spontaneous bleeding, soft tissue or joint bleeding, and severe subcutaneous hematomas [2]. According to the Centers for Disease Control and Prevention (CDC) in the United States, severe Hemophilia B patients account for 30%-40% of all diagnosed patients [3].
The F9 gene encodes coagulation factor IX, a vitamin K-dependent serine protease that plays a key role in the intrinsic coagulation pathway. Factor IX circulates in the blood as an inactive zymogen and is converted to its active form, factor IXa, by the cleavage of its activation peptide by factor XIa. Factor IXa then interacts with Ca2+ ions, membrane phospholipids, and factor Ⅷ to activate factor X in the coagulation cascade. The body can normally stop bleeding when the levels of factors Ⅷ and IX are ≥50% of normal values [4]. The deficiency of the F9 gene can lead to a clotting disorder with insufficient factor IX, causing X-linked recessive hemophilia B.
F9-KO mice are Hemophilia B disease models constructed by knocking out the mouse F9 gene. F9-KO mice lack F9 mRNA expression and exhibit coagulation dysfunction and other Hemophilia B-related phenotypes. They can be used to study the genetic mechanisms and clinical phenotypes of Hemophilia B in humans and to assist in developing, screening, and evaluating therapeutic drugs. The homozygotes are viable and fertile. Tail docking may lead to significant bleeding. Immediate hemostasis, such as cauterizing the tail incision, is advised to prevent health complications in homozygous mice. Usually, ear tags are applied to mice at 2 to 3 weeks of age (a small notch is made with scissors for identification). After tail clipping for genotyping, the tail wound should be promptly cauterized (using metal forceps heated with an alcohol lamp) to prevent fatal bleeding. Following cauterization, place the mouse in a clean cage to prevent wound infection and add environmental enrichment.
Hemophilia is a group of genetic bleeding disorders that affect the blood’s ability to clot. The common feature of this disease is the generation of abnormal clotting factors, which leads to prolonged clotting time and increased risk of bleeding after minor injuries. In severe cases, spontaneous bleeding can occur even without obvious trauma. As an X-linked recessive disorder, Hemophilia B is more common in males, with approximately 1 in every 30,000 newborn males worldwide being affected [1]. Hemophilia B is caused by mutations in the F9 (FIX) gene, which leads to a deficiency of clotting factor IX. The severity of the disease is usually correlated with the activity level of factor IX in the blood plasma. Mild patients (IX factor activity >5%, >0.05 IU/mL) do not experience spontaneous bleeding, but the amount of bleeding after injury or surgery may increase. Moderate patients (IX factor activity 1%-5%, 0.01-0.05 IU/mL) rarely experience spontaneous bleeding, but even minor injuries can cause prolonged bleeding. Severe patients (IX factor activity <1%, <0.01 IU/mL) experience spontaneous bleeding, soft tissue or joint bleeding, and severe subcutaneous hematomas [2]. According to the Centers for Disease Control and Prevention (CDC) in the United States, severe Hemophilia B patients account for 30%-40% of all diagnosed patients [3].
The F9 gene encodes coagulation factor IX, a vitamin K-dependent serine protease that plays a key role in the intrinsic coagulation pathway. Factor IX circulates in the blood as an inactive zymogen and is converted to its active form, factor IXa, by the cleavage of its activation peptide by factor XIa. Factor IXa then interacts with Ca2+ ions, membrane phospholipids, and factor Ⅷ to activate factor X in the coagulation cascade. The body can normally stop bleeding when the levels of factors Ⅷ and IX are ≥50% of normal values [4]. The deficiency of the F9 gene can lead to a clotting disorder with insufficient factor IX, causing X-linked recessive hemophilia B.
F9-KO mice are Hemophilia B disease models constructed by knocking out the mouse F9 gene. F9-KO mice lack F9 mRNA expression and exhibit coagulation dysfunction and other Hemophilia B-related phenotypes. They can be used to study the genetic mechanisms and clinical phenotypes of Hemophilia B in humans and to assist in developing, screening, and evaluating therapeutic drugs. The homozygotes are viable and fertile. Tail docking may lead to significant bleeding. Immediate hemostasis, such as cauterizing the tail incision, is advised to prevent health complications in homozygous mice. Usually, ear tags are applied to mice at 2 to 3 weeks of age (a small notch is made with scissors for identification). After tail clipping for genotyping, the tail wound should be promptly cauterized (using metal forceps heated with an alcohol lamp) to prevent fatal bleeding. Following cauterization, place the mouse in a clean cage to prevent wound infection and add environmental enrichment.
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