公开(公告)号：US06492137B1

公开(公告)日：2002-12-10

申请号：US07672530

申请日：1991-03-19

申请人： Henry M. Sucov ,  Ronald M. Evans ,  Kazuhiko Umesono

发明人： Henry M. Sucov ,  Ronald M. Evans ,  Kazuhiko Umesono

IPC分类号： C12P2102

CPC分类号： C07K14/70567 ,  C07K14/721 ,  C12N15/85 ,  C12N2800/108 ,  C12N2830/002 ,  C12N2830/008 ,  C12N2830/30 ,  C12N2830/38 ,  C12N2830/60 ,  C12N2830/85 ,  C12Q1/6897 ,  G01N33/5008 ,  G01N33/502 ,  G01N33/5023 ,  G01N33/5041 ,  G01N33/743

摘要： DNA segments have been discovered, and characterized by sequence, which are response elements operative to confer responsiveness to ligands for several members of the steroid/thyroid superfamily of receptors, for the transcriptional activation and/or repression of promoters in cells. By using transcriptional control regions comprising response elements of the present invention in combination with a functional promoter, it is now possible to provide recombinant DNA vectors containing a gene, the transcription (and, thereby, also expression) of which is under the control of a promoter, the transcriptional activity of which is responsive to ligands for members of the steroid/thyroid superfamily of receptors.

摘要翻译： 已经发现了DNA区段，其特征在于序列，其是作用于赋予类固醇/甲状腺超家族受体的若干成员对配体的反应性的响应元件，用于细胞中启动子的转录激活和/或抑制。 通过使用包含本发明的响应元件与功能启动子组合的转录控制区，现在可以提供含有基因的重组DNA载体，其转录（并且由此也由其表达）处于一个 启动子，其转录活性对受体的类固醇/甲状腺超家族成员的配体有反应。

公开(公告)号：US5091518A

公开(公告)日：1992-02-25

申请号：US438757

申请日：1989-11-16

申请人： Henry M. Sucov ,  Ronald M. Evans

发明人： Henry M. Sucov ,  Ronald M. Evans

IPC分类号： C07H21/04 ,  C07K14/705 ,  C12N5/10 ,  C12N15/09 ,  C12N15/85 ,  C12Q1/02 ,  G01N33/50 ,  G01N33/74

CPC分类号： G01N33/5023 ,  C07K14/70567 ,  C12N15/85 ,  G01N33/5008 ,  G01N33/743 ,  C12N2830/002 ,  C12N2830/60 ,  C12N2830/85

摘要： The present invention provide transcriptional control regions, expression vectors comprising said regions, mammalian cells transformed to transcribe and express genes from said vectors, and various methods of assaying compounds for hormone agonist or antagonist activity, all based on discovery of response elements of the .beta.-retinoic acid receptor and of the activation of said response elements in all mammalian cells without need to transform the cells to express the receptor independently of endogenous expression thereof.

摘要翻译： 本发明提供了转录控制区，包含所述区域的表达载体，转化成转录和表达来自所述载体的基因的哺乳动物细胞，以及各种测定激素激动剂或拮抗剂活性化合物的方法，所有这些都是基于β - 视黄酸受体和所有哺乳动物细胞中所述应答元件的活化，而不需要转化细胞以独立于其内源性表达而表达受体。

公开(公告)号：US07189510B2

公开(公告)日：2007-03-13

申请号：US10302557

申请日：2002-11-22

申请人： Henry M. Sucov ,  Ronald M. Evans ,  Kazuhiko Umesono

发明人： Henry M. Sucov ,  Ronald M. Evans ,  Kazuhiko Umesono

IPC分类号： C12Q1/68

CPC分类号： C07K14/70567 ,  C07K14/721 ,  C12N15/85 ,  C12N2800/108 ,  C12N2830/002 ,  C12N2830/008 ,  C12N2830/30 ,  C12N2830/38 ,  C12N2830/60 ,  C12N2830/85 ,  C12Q1/6897 ,  G01N33/5008 ,  G01N33/502 ,  G01N33/5023 ,  G01N33/5041 ,  G01N33/743

摘要： DNA segments have been discovered, and characterized by sequence, which are response elements operative to confer responsiveness to ligands for several members of the steroid/thyroid superfamily of receptors, for the transcriptional activation and/or repression of promoters in cells. By using transcriptional control regions comprising response elements of the present invention in combination with a functional promoter, it is now possible to provide recombinant DNA vectors containing a gene, the transcription (and, thereby, also expression) of which is under the control of a promoter, the transcriptional activity of which is responsive to ligands for members of the steroid/thyroid superfamily of receptors.

摘要翻译： 已经发现了DNA区段，其特征在于序列，其是作用于赋予类固醇/甲状腺超家族受体的若干成员对配体的反应性的响应元件，用于细胞中启动子的转录激活和/或抑制。 通过使用包含本发明的响应元件与功能启动子组合的转录控制区，现在可以提供含有基因的重组DNA载体，其转录（并且由此也由其表达）处于一个 启动子，其转录活性对受体的类固醇/甲状腺超家族成员的配体有反应。

公开(公告)号：US06278040B1

公开(公告)日：2001-08-21

申请号：US08802468

申请日：1997-02-19

申请人： Henry M. Sucov ,  Ronald M. Evans ,  Kenneth R. Chien

发明人： Henry M. Sucov ,  Ronald M. Evans ,  Kenneth R. Chien

IPC分类号： C12N1509

CPC分类号： C12N15/8509 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0375 ,  A61K31/203 ,  A61K49/0008

摘要： In accordance with the present invention, there are provided targeted loss of function mutant mice which express less than endogenous levels of at least one member of the steroid/thyroid superfamily of receptors in at least one specific tissue type. For example, mutations in the RXR&agr; gene in mouse germlines are lethal in the embryonic stage between E13.5 and E16.5 when bred to homozygosity. The major defect responsible for this lethal effect is hypoplastic development of the ventricular chambers of the heart, which is manifest as a grossly thinned ventricular wall with concurrent defects in ventricular septation. This phenotype is identical to a subset of the effects of embryonic vitamin A deficiency, and therefore establishes RXR&agr; as a genetic component of the vitamin A signaling pathway in cardiac morphogenesis. The cardiac outflow tracts and associated vessels, which are populated by derivatives of the neural crest and which are also sensitive to vitamin A deficiency, are normal in homozygous embryos, indicating the genetic independence of ventricular chamber development. Hepatic differentiation was dramatically but transiently retarded, yet is histologically and morphologically normal. These results ascribe an essential function for the RXR&agr; gene in embryonic development, and provide the first evidence of a requirement for RXR in one of its predicted hormone response pathways.

摘要翻译： 根据本发明，提供了在至少一种特定组织类型中表达低于受体的类固醇/甲状腺超家族的至少一种成员的内源水平的功能突变小鼠的靶向丧失。 例如，当培育成纯合子时，E13.5和E16.5之间的胚胎阶段，小鼠种系中RXRalpha基因的突变是致命的。 负责这种致死作用的主要缺陷是心脏心室的发育不良，这表现为心室隔膜同时缺陷的严重变薄的心室壁。 这种表型与胚胎维生素A缺乏症的一个亚组相同，因此在心脏形态发生中建立了RXRalpha作为维生素A信号通路的遗传成分。 由神经嵴的衍生物填充并且对维生素A缺乏敏感的心脏流出道和相关血管在纯合胚中是正常的，表明心室发育的遗传独立性。 肝分化显着但短暂延迟，但组织学和形态学正常。 这些结果归因于胚胎发育中RXRalpha基因的基本功能，并提供了其预测的激素反应途径之一的RXR要求的第一个证据。