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    • 1. 发明申请
    • Genetically Modified Rat Models for Cytokine-Cytokine Signaling Pathways
    • 细胞因子 - 细胞因子信号通路的转基因大鼠模型
    • US20110023142A1
    • 2011-01-27
    • US12842418
    • 2010-07-23
    • Eric M. OstertagJohn Stuart Crawford
    • Eric M. OstertagJohn Stuart Crawford
    • G01N33/00A01K67/027C12Q1/02
    • C12N15/8509A01K67/0276A01K2217/075A01K2227/105A01K2267/0325A01K2267/0368
    • The present invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of gene(s) or gene product(s) resulting in cytokine-cytokine mediated autoimmune and inflammatory disease. In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human autoimmune and inflammatory disease and methods of their use. Specifically, the invention pertains to a genetically altered rat, or a rat cell in culture, that is defective in at least one of two alleles of a cytokine gene such as the Faslg gene, the Fas gene, etc. In one embodiment, the cytokine gene is the Faslg gene. In another embodiment, the cytokine gene is one of several known cytokine genes, such as Fas, IFNγ, TNF-α, IL-2, IL-10, and IL-12. The inactivation of at least one of these cytokine alleles results in an animal with a higher susceptibility to cytokine-cytokine mediated autoimmune and inflammatory disease induction. In one embodiment, the genetically altered animal is a rat of this type and is able to serve as a useful model for cytokine-cytokine mediated autoimmune and inflammatory disease and as a test animal for autoimmune and other studies.
    • 本发明涉及由于导致细胞因子 - 细胞因子介导的自身免疫和炎性疾病的基因或基因产物的破坏而缺陷的动物细胞,优选哺乳动物,更优选大鼠的工程。 另一方面,本发明涉及基因修饰的大鼠,以及这些动物的后裔和祖先,其是人自身免疫和炎性疾病的动物模型及其使用方法。 具体地,本发明涉及在细胞因子基因的两个等位基因中的至少一个中的遗传改变的大鼠或培养物中的大鼠细胞,如Faslg基因,Fas基因等。在一个实施方案中,细胞因子 基因是Faslg基因。 在另一个实施方案中,细胞因子基因是几种已知的细胞因子基因之一,例如Fas,IFNγ,TNF-α,IL-2,IL-10和IL-12。 这些细胞因子等位基因中的至少一种的失活导致对细胞因子 - 细胞因子介导的自身免疫和炎性疾病诱导具有较高敏感性的动物。 在一个实施方案中,遗传改变的动物是这种类型的大鼠,并且能够用作细胞因子 - 细胞因子介导的自身免疫和炎性疾病的有用模型,并且作为自身免疫和其他研究的测试动物。
    • 6. 发明申请
    • Genetically Modified Rat Models for Drug Metabolism
    • 用于药物代谢的转基因大鼠模型
    • US20110035816A1
    • 2011-02-10
    • US12850921
    • 2010-08-05
    • Eric M. OstertagJohn Stuart Crawford
    • Eric M. OstertagJohn Stuart Crawford
    • G01N33/68A01K67/027C12Q1/02
    • A01K67/0276A01K2207/05A01K2217/075A01K2217/15A01K2227/105A01K2267/03C07K14/705C12N15/8509C12N2800/90G01N33/94G01N2500/04G01N2500/10
    • The present invention provides a desired rat or a rat cell which contains a predefined, specific and desired alteration rendering the rat or rat cell predisposed to alterations in drug and chemical metabolism by modification of its structure or mechanism. Specifically, the invention pertains to a genetically altered rat, or a rat cell in culture, that is defective in at least one of two alleles of a drug metabolism gene such as the Cyp7b1 gene, the Cyp3a4 gene, etc. In another embodiment, the rat cell is a somatic cell. The inactivation of at least one drug metabolism allele results in an animal with a higher susceptibility to altered drug and chemical metabolism. In one embodiment, the genetically altered animal is a rat of this type and is able to serve as a useful model for altered drug and chemical metabolism or toxicology and as a test animal for autoimmune and other studies. The invention additionally pertains to the use of such rats or rat cells, and their progeny in research and medicine. In one embodiment, the invention provides a genetically modified or chimeric rat cell whose genome comprises two chromosomal alleles of a drug metabolism gene wherein at least one of the two alleles contains a mutation, or the progeny of the cell.
    • 本发明提供了期望的大鼠或大鼠细胞,其包含预定义的特异性和期望的改变,使得大鼠或大鼠细胞易于改变其结构或机制而改变药物和化学代谢。 具体地说,本发明涉及在诸如Cyp7b1基因,Cyp3a4基因等药物代谢基因的两个等位基因中的至少一个中缺失的基因改变的大鼠或培养物中的大鼠细胞。在另一个实施方案中, 大鼠细胞是体细胞。 至少一种药物代谢等位基因的失活导致对改变的药物和化学代谢具有较高敏感性的动物。 在一个实施方案中,遗传改变的动物是这种类型的大鼠,并且能够用作改变的药物和化学代谢或毒理学的有用模型,并且作为用于自身免疫和其他研究的测试动物。 本发明还涉及这些大鼠或大鼠细胞及其后代在研究和医学中的应用。 在一个实施方案中,本发明提供了遗传修饰或嵌合的大鼠细胞,其基因组包含药物代谢基因的两个染色体等位基因,其中两个等位基因中的至少一个含有突变或细胞的后代。
    • 9. 发明授权
    • Genetically modified rat comprising a cytokine gene disruption and exhibiting a greater susceptibility to a cytokine-mediated autoimmune and/or inflammatory disease
    • 包含细胞因子基因破坏并且对细胞因子介导的自身免疫和/或炎性疾病表现出更大易感性的转基因大鼠
    • US08558055B2
    • 2013-10-15
    • US12842418
    • 2010-07-23
    • Eric M. OstertagJohn Stuart Crawford
    • Eric M. OstertagJohn Stuart Crawford
    • C12N15/00A01K67/033A01K67/027G01N33/00
    • C12N15/8509A01K67/0276A01K2217/075A01K2227/105A01K2267/0325A01K2267/0368
    • The present invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of gene(s) or gene product(s) resulting in cytokine-cytokine mediated autoimmune and inflammatory disease. In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human autoimmune and inflammatory disease and methods of their use. Specifically, the invention pertains to a genetically altered rat, or a rat cell in culture, that is defective in at least one of two alleles of a cytokine gene such as the Faslg gene, the Fas gene, etc. In one embodiment, the cytokine gene is the Faslg gene. In another embodiment, the cytokine gene is one of several known cytokine genes, such as Fas, IFNγ, TNF-α, IL-2, IL-10, and IL-12. The inactivation of at least one of these cytokine alleles results in an animal with a higher susceptibility to cytokine-cytokine mediated autoimmune and inflammatory disease induction. In one embodiment, the genetically altered animal is a rat of this type and is able to serve as a useful model for cytokine-cytokine mediated autoimmune and inflammatory disease and as a test animal for autoimmune and other studies.
    • 本发明涉及由于导致细胞因子 - 细胞因子介导的自身免疫和炎性疾病的基因或基因产物的破坏而缺陷的动物细胞,优选哺乳动物,更优选大鼠的工程。 另一方面,本发明涉及基因修饰的大鼠,以及这些动物的后裔和祖先,其是人自身免疫和炎性疾病的动物模型及其使用方法。 具体地,本发明涉及在细胞因子基因的两个等位基因中的至少一个中的遗传改变的大鼠或培养物中的大鼠细胞,如Faslg基因,Fas基因等。在一个实施方案中,细胞因子 基因是Faslg基因。 在另一个实施方案中,细胞因子基因是几种已知的细胞因子基因之一,例如Fas,IFNgamma,TNF-α,IL-2,IL-10和IL-12。 这些细胞因子等位基因中的至少一种的失活导致对细胞因子 - 细胞因子介导的自身免疫和炎性疾病诱导具有较高敏感性的动物。 在一个实施方案中,遗传改变的动物是这种类型的大鼠,并且能够用作细胞因子 - 细胞因子介导的自身免疫和炎性疾病的有用模型,并且作为自身免疫和其他研究的测试动物。