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1. 发明授权

US06492137B1 Response element compositions and assays employing same 失效
标题翻译：响应元素组合物和采用其的测定法
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。

2. 发明授权

US07189510B2 Response element compositions and assays employing same 失效
标题翻译：响应元素组合物和采用其的测定法
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。

3. 发明授权

US5091518A Beta retinoic acid response elements compositions and assays 失效
标题翻译： BETA反应性反应元素组合物和测定
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。

4. 发明授权

US06278040B1 Receptor-deficient mice and cell lines derived therefrom, and uses thereof 失效
标题翻译：受体缺陷小鼠和由其衍生的细胞系及其用途
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。

5. 发明授权

US06458926B1 Heterodimer complex of RXR and NURR1 or NGFI-B 失效
标题翻译： RXR和NURR1或NGFI-B的异二聚体复合物
公开(公告)号：US06458926B1
公开(公告)日：2002-10-01
申请号：US08877966
申请日：1997-06-18
申请人： Ronald M. Evans , Barry M. Forman , Kazuhiko Umesono
发明人： Ronald M. Evans , Barry M. Forman , Kazuhiko Umesono
IPC分类号： C07K14435
CPC分类号： C07K14/70567 , C07K2319/00 , G01N33/6875 , G01N33/74
摘要： Heterodimerization is a common paradigm among eucaryotic transcription factors, though it remains unclear how individual monomers contribute to the overall transcriptional activities of the complex. The 9-cis retinoic acid receptor (RXR) serves as a common heterodimerization partner for several nuclear receptors including the thyroid hormone (T3R), retinoic acid (RAR) and vitamin D receptors. A strategy has been devised to examine the transcriptional properties of each receptor individually or when tethered to a heterodimeric partner. It has been found that the intrinsic activity of RXR is masked in RXR-T3R and RXR-RAR heterodimers. In contrast, a novel RXR-Nurr1 heterodimer described herein is highly responsive to RXR ligands, suggesting that different partners exert unique allosteric control over the RXR response. These findings establish a novel 9-cis retinoic acid response pathway and resolve the paradox as to how T3R, RAR and VDR contribute to distinct physiologic pathways while sharing a common RXR subunit.
摘要翻译：异源二聚化是真核转录因子中的常见范例，尽管单个单体如何有助于复合物的整体转录活性仍不清楚。 9-顺式视黄酸受体（RXR）用作几种核受体（包括甲状腺激素（T3R），视黄酸（RAR）和维生素D受体）的常见异源二聚体配偶体。已经设计出一种策略来单独检测每个受体的转录特性，或者当连接到异二聚体配偶体时。已经发现在RXR-T3R和RXR-RAR异二聚体中RXR的固有活性被掩蔽。相比之下，本文描述的新型RXR-Nurr1异源二聚体对RXR配体具有高度响应性，表明不同的合作伙伴对RXR应答发挥独特的变构控制。这些研究结果建立了一种新的9-顺式视黄酸反应途径，并解决了T3R，RAR和VDR如何在共享一个共同的RXR亚基时对不同的生理途径有贡献的矛盾。

6. 发明授权

US5530094A Gamma retinoic acid receptor 失效
标题翻译： γ视黄酸受体
公开(公告)号：US5530094A
公开(公告)日：1996-06-25
申请号：US100039
申请日：1993-07-30
申请人： Fumimaro Takaku , Takashi Ishikawa , Michio Imawari , Ronald M. Evans , Kazuhiko Umesono
发明人： Fumimaro Takaku , Takashi Ishikawa , Michio Imawari , Ronald M. Evans , Kazuhiko Umesono
IPC分类号： A61K38/00 , C07K14/00 , C07K14/705 , C07K14/72 , C07K19/00 , C12N5/10 , C12N15/09 , C12P21/02 , C12R1/91 , C07G1/00 , C12N15/00 , C12P21/06
CPC分类号： C07K14/72 , C07K14/70567 , C07K14/721 , A61K38/00 , C07K2319/00 , C07K2319/715 , C07K2319/80 , Y10S530/826 , Y10S530/846
摘要： A novel gamma retinoic acid receptor is disclosed. The novel receptor is encoded for by cDNA carried on plasmid pGEM-hRAR.gamma., which has been deposited with the American Type Culture Collection for patent purposes. Chimeric receptor proteins are also disclosed. The chimera contain at least one functional domain from the new gamma retinoic acid receptor.
摘要翻译：公开了一种新型的视黄酸受体。新型受体由携带在质粒pGEM-hRARγ上的cDNA编码，其已经保藏在美国典型培养物保藏中心用于专利。还公开了嵌合受体蛋白。嵌合体含有来自新的视黄酸受体的至少一个功能结构域。

7. 发明授权

US5548063A Retinoic acid receptor alpha proteins 失效
标题翻译：视黄酸受体α蛋白
公开(公告)号：US5548063A
公开(公告)日：1996-08-20
申请号：US179912
申请日：1994-01-11
申请人： Ronald M. Evans , Estelita S. Ong , Prudimar S. Segui , Catherine C. Thompson , Kazuhiko Umesono , Vincent Giguere
发明人： Ronald M. Evans , Estelita S. Ong , Prudimar S. Segui , Catherine C. Thompson , Kazuhiko Umesono , Vincent Giguere
IPC分类号： C07K14/705 , C12Q1/68
CPC分类号： C12Q1/6897 , C07K14/70567 , C07K2319/00 , C07K2319/61 , C07K2319/715 , C07K2319/81
摘要： A human retinoic acid receptor alpha protein is disclosed. The receptor is encoded by the cDNA insert of plasmid phRAR1, which has been deposited with ATCC. Methods employing chimeric receptors derived from the retinoic acid receptor are illustrated which demonstrate that the ligand for the new receptor is the retinoid, retinoic acid.
摘要翻译：公开了人视黄酸受体α蛋白。受体由已经保藏于ATCC的质粒phRAR1的cDNA插入片段编码。示出了使用衍生自视黄酸受体的嵌合受体的方法，其表明新受体的配体是类视黄醇维甲酸。

8. 发明授权

US5274077A Retinoic acid receptor composition 失效
标题翻译：视黄酸受体组成
公开(公告)号：US5274077A
公开(公告)日：1993-12-28
申请号：US975777
申请日：1992-11-13
申请人： Ronald M. Evans , Estelita S. Ong , Prudimar S. Segui , Catherine C. Thompson , Kazuhiko Umesono , Vincent Giguere
发明人： Ronald M. Evans , Estelita S. Ong , Prudimar S. Segui , Catherine C. Thompson , Kazuhiko Umesono , Vincent Giguere
IPC分类号： C07K14/705 , C12N15/12 , C12Q1/68 , C07K13/00
CPC分类号： C07K14/70567 , C12Q1/6897 , C07K2319/61 , C07K2319/715 , C07K2319/81
摘要： A novel retinoic acid receptor is disclosed. The novel receptor is encoded for by CDNA carried on plasmid phRAR1, which has been deposited with the American Type Culture Collection for patent purposes. Chimeric receptor proteins are also disclosed. The chimera are constructed by exchanging functional domains between the glucocorticoid, the mineralocorticoid, the estrogen-related, the thyroid and the retinoic acid receptors. In addition, a novel method for identifying functional ligands for receptor proteins is disclosed. The method, which takes advantage of the modular structure of the hormone receptors and the idea that the functional domains may be interchangeable, replaces the DNA-binding domain of a putative novel receptor with the DNA-binding domain of a known receptor such as the glucocorticoid receptor. The resulting chimeric construction, when expressed in cells, produces a hybrid receptor whose activation of a ligand--(e.g., glucocorticoid) inducible promoter is dependent on the presence of the new ligand. The novel method is illustrated in part by showing that the ligand for the new receptor protein is the retinoid, retinoic acid.
摘要翻译：公开了一种新型视黄酸受体。新型受体由携带在质粒phRAR1上的CDNA编码，其已经用美国典型培养物保藏中心专利保藏。还公开了嵌合受体蛋白。通过在糖皮质激素，盐皮质激素，雌激素相关，甲状腺和视黄酸受体之间交换功能结构来构建嵌合体。另外，公开了用于鉴定受体蛋白质的功能性配体的新方法。利用激素受体的模块化结构的方法和功能域可以互换的想法将已知受体的DNA结合结构域（例如糖皮质激素）替代推定的新受体的DNA结合结构域受体。当在细胞中表达时，产生的嵌合构型产生杂合受体，其配体（例如，糖皮质激素）诱导型启动子的活化取决于新配体的存在。该新方法部分地通过显示新受体蛋白质的配体是类视黄醇，视黄酸来说明。

9. 发明授权

US5597693A Hormone response element compositions and assay 失效
标题翻译：激素反应元件组成和测定
公开(公告)号：US5597693A
公开(公告)日：1997-01-28
申请号：US494618
申请日：1990-03-16
申请人： Ronald M. Evans , Kazuhiko Umesono
发明人： Ronald M. Evans , Kazuhiko Umesono
IPC分类号： C07K7/06 , C07K14/00 , C07K14/435 , C07K14/705 , C07K14/72 , C12N15/09 , C12P21/02 , C12Q1/68 , C12R1/91
CPC分类号： C12Q1/6897 , C07K14/721
摘要： The present invention discloses steroid/thyroid hormone receptor DNA binding domain compositions that determine target gene specificity. The invention further discloses methods converting the target gene specificity of one receptor into the target gene specificity of another. Still further the invention discloses novel assays for identifying ligands for orphan hormone receptors. These assays are especially useful since they avoid the necessity of constructing chimeric genes and proteins in order to search for ligands that can activate a putative receptor.
摘要翻译：本发明公开了确定靶基因特异性的类固醇/甲状腺激素受体DNA结合结构域组合物。本发明还公开了将一种受体的靶基因特异性转化为另一种受体的靶基因特异性的方法。本发明进一步公开了用于鉴定孤儿激素受体配体的新型测定法。这些测定是特别有用的，因为它们避免了构建嵌合基因和蛋白质的需要，以便搜索可以激活推定受体的配体。

10. 发明授权

US5260432A Human gamma retinoic acid receptor DNA 失效
标题翻译：人类视网膜酸受体DNA
公开(公告)号：US5260432A
公开(公告)日：1993-11-09
申请号：US370407
申请日：1989-06-22
申请人： Fumimaro Takaku , Takashi Ishikawa , Michio Imawari , Ronald M. Evans , Kazuhiko Umesono
发明人： Fumimaro Takaku , Takashi Ishikawa , Michio Imawari , Ronald M. Evans , Kazuhiko Umesono
IPC分类号： A61K38/00 , C07K14/00 , C07K14/705 , C07K14/72 , C07K19/00 , C12N5/10 , C12N15/09 , C12P21/02 , C12R1/91 , C07H21/04 , C07H21/02 , C12Q1/68
CPC分类号： C07K14/72 , C07K14/70567 , C07K14/721 , A61K38/00 , C07K2319/00 , C07K2319/715 , C07K2319/80 , Y10S530/826 , Y10S530/846
摘要： A novel gamma retinoic acid receptor is disclosed. The novel receptor is encoded for by cDNA carried on plasmid pGEM-hRAR.gamma., which has been deposited with the American Type Culture Collection for patent purposes. Chimeric receptor proteins are also disclosed. The chimera contain at least one functional domain from the new gamma retinoic acid receptor.
摘要翻译：公开了一种新型的视黄酸受体。新型受体由携带在质粒pGEM-hRARγ上的cDNA编码，其已经保藏在美国典型培养物保藏中心用于专利。还公开了嵌合受体蛋白。嵌合体含有来自新的视黄酸受体的至少一个功能结构域。

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