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    Methods for producing tetracycline-regulated transgenic mice
    33.
    发明授权
    Methods for producing tetracycline-regulated transgenic mice 失效
    生产四环素调节转基因小鼠的方法

    公开(公告)号：US5922927A

    公开(公告)日：1999-07-13

    申请号：US897719

    申请日：1997-07-21

    申请人： Hermann Bujard ,  Manfred Gossen ,  Jochen G. Salfeld ,  Jeffrey W. Voss

    发明人： Hermann Bujard ,  Manfred Gossen ,  Jochen G. Salfeld ,  Jeffrey W. Voss

    IPC分类号： A01K67/027 ,  A61K48/00 ,  C07K14/00 ,  C12N5/08 ,  C12N5/10 ,  C12N15/00 ,  C12N15/09 ,  C12N15/31 ,  C12N15/62 ,  C12N15/63 ,  C12N15/85 ,  C12R1/91 ,  C12N5/00

    CPC分类号： A01K67/0275 ,  C12N15/62 ,  C12N15/635 ,  C12N15/85 ,  A01K2217/05 ,  A01K2217/075 ,  C07K2319/09 ,  C07K2319/61 ,  C07K2319/71 ,  C07K2319/80 ,  C12N2830/006

    摘要： Transgenic mice carrying two transgenes, the first coding for a transactivator fusion protein comprising a tet repressor and a polypeptide which directly or indirectly activates in eucaryotic cells, and the second comprising a gene operably linked to a minimal promoter operably linked to at least one tet operator sequence, are disclosed. Isolated DNA molecules (e.g., targeting vectors) for integrating a polynucleotide sequence encoding a transactivator of the invention at a predetermined location within a second target DNA molecule by homologous recombination are also disclosed. Transgenic mice having the DNA molecules of the invention integrated at a predetermined location in a chromosome by homologous recombination are also encompassed by the invention. Methods to regulate the expression of a tet operator linked-gene of interest by administering tetracycline or a tetracycline analogue to a mouse of the invention are also disclosed. The regulatory system of the invention allows for conditional inactivation or modulation of expression of a gene of interest in a host cell or mouse.

    摘要翻译： 携带两个转基因的转基因小鼠，首先编码包含直接或间接在真核细胞中活化的tet阻遏物和多肽的反式激活因子融合蛋白，第二编码包含与可操作地连接至少一个tet操纵子的最小启动子可操作地连接的基因 序列。 还公开了通过同源重组将编码本发明的反式激活物的多核苷酸序列整合到第二靶DNA分子内的预定位置的分离的DNA分子（例如靶向载体）。 通过同源重组将具有整合在染色体中预定位置的本发明的DNA分子的转基因小鼠也包括在本发明中。 还公开了通过向本发明的小鼠施用四环素或四环素类似物来调节目的基因的表达的方法。 本发明的调节系统允许在宿主细胞或小鼠中条件性失活或调控感兴趣的基因的表达。

    Mice transgenic for a tetracycline-controlled transcriptional activator
    34.
    发明授权
    Mice transgenic for a tetracycline-controlled transcriptional activator 失效
    用于四环素控制的转录激活子的转基因小鼠

    公开(公告)号：US5859310A

    公开(公告)日：1999-01-12

    申请号：US481970

    申请日：1995-06-07

    申请人： Hermann Bujard ,  Manfred Gossen ,  Jochen G. Salfeld ,  Jeffrey W. Voss

    发明人： Hermann Bujard ,  Manfred Gossen ,  Jochen G. Salfeld ,  Jeffrey W. Voss

    IPC分类号： A01K67/027 ,  A61K48/00 ,  C12N5/08 ,  C12N15/62 ,  C12N15/63 ,  C12N15/85 ,  C12N5/00 ,  C12N15/00 ,  C12N15/09

    CPC分类号： C12N15/62 ,  A01K67/0275 ,  C12N15/635 ,  C12N15/85 ,  A01K2217/05 ,  A01K2217/075 ,  C07K2319/09 ,  C07K2319/61 ,  C07K2319/71 ,  C07K2319/80 ,  C12N2830/006

    摘要： Transgenic mice carrying two transgenes, the first coding for a transactivator fusion protein comprising a tet repressor and a polypeptide which directly or indirectly activates transcription of a tet operator-linked gene in eucaryotic cells, and the second comprising a gene operably linked to a minimal promotor operably linked to at least one tet operator sequence, are disclosed. Isolated DNA molecules (e.g., targeting vectors) for integrating a polynucleotide sequence encoding a transactivator of the invention at a predetermined location within a second target DNA molecule by homologous recombination are also disclosed. Transgenic mice having the DNA molecules of the invention integrated at a predetermined location in a chromosome by homologous recombination are also encompassed by the invention. Methods to regulate the expression of a tet operator linked-gene of interest by administering tetracycline or a tetracycline analogue to a mouse of the invention are also disclosed. The regulatory system of the invention allows for conditional inactivation or modulation of expression of a gene of interest in a host cell or mouse.

    摘要翻译： 携带两个转基因的转基因小鼠，首先编码包含tet阻遏物的反式激活因子融合蛋白，以及直接或间接激活真核细胞中与tet操纵子连接的基因的转录的多肽，第二编码包含可操作地连接到最小启动子的基因 可操作地连接至至少一个tet操纵子序列。 还公开了通过同源重组将编码本发明的反式激活物的多核苷酸序列整合到第二靶DNA分子内的预定位置的分离的DNA分子（例如靶向载体）。 通过同源重组将具有整合在染色体中预定位置的本发明的DNA分子的转基因小鼠也包括在本发明中。 还公开了通过向本发明的小鼠施用四环素或四环素类似物来调节目的基因的表达的方法。 本发明的调节系统允许在宿主细胞或小鼠中条件性失活或调控感兴趣的基因的表达。

    Methods for regulating gene expression
    38.
    发明授权
    Methods for regulating gene expression 失效
    调节基因表达的方法

    公开(公告)号：US06783756B2

    公开(公告)日：2004-08-31

    申请号：US09281674

    申请日：1999-03-30

    申请人： Hermann Bujard ,  Manfred Gossen ,  Jochen G. Salfeld ,  Jeffrey W. Voss

    发明人： Hermann Bujard ,  Manfred Gossen ,  Jochen G. Salfeld ,  Jeffrey W. Voss

    IPC分类号： A61K6300

    CPC分类号： C12N15/62 ,  A01K67/0275 ,  A01K2217/05 ,  A01K2217/075 ,  C07K2319/09 ,  C07K2319/61 ,  C07K2319/71 ,  C07K2319/80 ,  C12N15/635 ,  C12N15/85 ,  C12N2830/006

    摘要： A method for regulating expression of a tet operator-linked gene in a cell of a subject is disclosed. In one embodiment, the method involves introducing into the cell a nucleic acid molecule encoding a tetracycline-controllable transactivator (tTA), the tTA comprising a Tet repressor operably linked to a polypeptide which directly or indirectly activates transcription in eucaryotic cells; and modulating the concentration of a tetracycline, or analogue thereof, in the subject. Alternatively, in another embodiment, the method involves obtaining the cell from the subject, introducing into the cell a first nucleic acid molecule which operatively links a gene to at least one tet operator sequence, introducing into the cell a second nucleic acid molecule encoding a tTA, to form a modified cell, administering the modified cell to the subject, and modulating the concentration of a tetracycline, or analogue thereof, in the subject. The first and second nucleic acid molecule can be within a single molecule (e.g., in the same vector) or on separate molecules.

    摘要翻译： 公开了一种用于调节受试者细胞中tet操纵子连接基因表达的方法。 在一个实施方案中，所述方法包括将编码四环素可控反式激活因子（tTA）的核酸分子引入细胞，所述tTA包含可操作地连接到直接或间接激活真核细胞中的转录的多肽的Tet阻遏物; 并调节受试者中四环素或其类似物的浓度。 或者，在另一个实施方案中，所述方法包括从受试者获得细胞，向细胞中引入第一核酸分子，该第一核酸分子可操作地将基因连接至至少一个tet操纵子序列，将编码tTA的第二核酸分子 ，以形成修饰的细胞，向受试者施用修饰的细胞，并调节受试者中四环素或其类似物的浓度。 第一和第二核酸分子可以在单分子内（例如，在同一载体中）或分开的分子上。

    Transgenic organisms having tetracycline-regulated transcriptional regulatory systems
    39.
    发明授权
    Transgenic organisms having tetracycline-regulated transcriptional regulatory systems 有权
    具有四环素调节转录调控系统的转基因生物

    公开(公告)号：US06252136B1

    公开(公告)日：2001-06-26

    申请号：US09163269

    申请日：1998-09-29

    申请人： Hermann Bujard ,  Manfred Gossen ,  Jochen G. Salfeld ,  Jeffrey W. Voss

    发明人： Hermann Bujard ,  Manfred Gossen ,  Jochen G. Salfeld ,  Jeffrey W. Voss

    IPC分类号： C12N1509

    CPC分类号： C12N15/62 ,  A01K67/0275 ,  A01K2217/05 ,  A01K2217/075 ,  C07K2319/09 ,  C07K2319/61 ,  C07K2319/71 ,  C07K2319/80 ,  C12N15/635 ,  C12N15/85 ,  C12N2830/006

    摘要： Transgenic animals carrying two transgenes, the first coding for a transactivator fusion protein comprising a tet repressor and a polypeptide which directly or indirectly activates in eucaryotic cells, and the second comprising a gene operably linked to a minimal promoter operably linked to at least one tet operator sequence, are disclosed. Isolated DNA molecules (e.g., targeting vectors) for integrating a polynucleotide sequence encoding a transactivator of the invention at a predetermined location within a second target DNA molecule by homologous recombination are also disclosed. Transgenic animals having the DNA molecules of the invention integrated at a predetermined location in a chromosome by homologous recombination are also encompassed by the invention. Methods to regulate the expression of a tet operator linked-gene of interest by administering tetracycline or a tetracycline analogue to an animal of the invention are also disclosed. The regulatory system of the invention allows for conditional inactivation or modulation of expression of a gene of interest in a host cell or animal.

    摘要翻译： 携带两个转基因的转基因动物，第一编码包含直接或间接在真核细胞中活化的tet阻遏物和多肽的反式激活因子融合蛋白，第二编码包含与可操作地连接至少一个tet操纵子的最小启动子可操作地连接的基因 序列。 还公开了通过同源重组将编码本发明的反式激活物的多核苷酸序列整合到第二靶DNA分子内的预定位置的分离的DNA分子（例如靶向载体）。 通过同源重组将具有整合在染色体中预定位置的本发明的DNA分子的转基因动物也包括在本发明中。 还公开了通过向本发明的动物施用四环素或四环素类似物来调节所述目的基因的表达的方法。 本发明的调节系统允许在宿主细胞或动物中有条件地失活或调控感兴趣的基因的表达。

    Tight control of gene expression in eucaryotic cells by tetracycline-responsive promoters
    40.
    发明授权
    Tight control of gene expression in eucaryotic cells by tetracycline-responsive promoters 失效
    通过四环素响应启动子对真核细胞中基因表达的严格控制

    公开(公告)号：US5650298A

    公开(公告)日：1997-07-22

    申请号：US260452

    申请日：1994-06-14

    申请人： Hermann Bujard ,  Manfred Gossen ,  Jochen G. Salfeld ,  Jeffrey W. Voss

    发明人： Hermann Bujard ,  Manfred Gossen ,  Jochen G. Salfeld ,  Jeffrey W. Voss

    IPC分类号： A01K67/027 ,  A61K48/00 ,  C07K14/00 ,  C12N5/08 ,  C12N5/10 ,  C12N15/00 ,  C12N15/09 ,  C12N15/31 ,  C12N15/62 ,  C12N15/63 ,  C12N15/85 ,  C12R1/91 ,  C12P21/00 ,  C07H21/04

    CPC分类号： A01K67/0275 ,  C12N15/62 ,  C12N15/635 ,  C12N15/85 ,  A01K2217/05 ,  A01K2217/075 ,  C07K2319/09 ,  C07K2319/61 ,  C07K2319/71 ,  C07K2319/80 ,  C12N2830/006

    摘要： Transgenic animals carrying two transgenes, the first coding for a transactivator fusion protein comprising a tet repressor and a polypeptide which directly or indirectly activates in eucaryotic cells, and the second comprising a gene operably linked to a minimal promoter operably linked to at least one tet operator sequence, are disclosed. Isolated DNA molecules (e.g., targeting vectors) for integrating a polynucleotide sequence encoding a transactivator of the invention at a predetermined location within a second target DNA molecule by homologous recombination are also disclosed. Transgenic animals having the DNA molecules of the invention integrated at a predetermined location in a chromosome by homologous recombination are also encompassed by the invention. Methods to regulate the expression of a tet operator linked-gene of interest by administering tetracycline or a tetracycline analogue to an animal of the invention are also disclosed. The regulatory system of the invention allows for conditional inactivation or modulation of expression of a gene of interest in a host cell or animal.

    摘要翻译： 携带两个转基因的转基因动物，第一编码包含直接或间接在真核细胞中活化的tet阻遏物和多肽的反式激活因子融合蛋白，第二编码包含与可操作地连接至少一个tet操纵子的最小启动子可操作地连接的基因 序列。 还公开了通过同源重组将编码本发明的反式激活物的多核苷酸序列整合到第二靶DNA分子内的预定位置的分离的DNA分子（例如靶向载体）。 通过同源重组将具有整合在染色体中预定位置的本发明的DNA分子的转基因动物也包括在本发明中。 还公开了通过向本发明的动物施用四环素或四环素类似物来调节所述目的基因的表达的方法。 本发明的调节系统允许在宿主细胞或动物中有条件地失活或调控感兴趣的基因的表达。