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11. 发明申请

US20090007283A1 Transgenic Rodents Selectively Expressing Human B1 Bradykinin Receptor Protein 审中-公开
标题翻译：转基因啮齿动物选择性表达人B1缓激肽受体蛋白
公开(公告)号：US20090007283A1
公开(公告)日：2009-01-01
申请号：US10573926
申请日：2004-10-04
申请人： John W. Hess , Robert J. Gould , Douglas J. Pettibone , Thomas F. Vogt , Richard Z. Chen
发明人： John W. Hess , Robert J. Gould , Douglas J. Pettibone , Thomas F. Vogt , Richard Z. Chen
IPC分类号： A01K67/027
CPC分类号： A01K67/0275 , A01K2207/15 , A01K2217/00 , A01K2217/072 , A01K2227/105 , A01K2267/03 , C07K14/705 , C12N15/8509
摘要： Non-human transgenic animals, such as transgenic mice, are generated which incorporate the a non-native form of the bradykinin B1 receptor gene against a null phenotype for the native form of the bradykinin B1 receptor. An exemplified portion of the invention disclosed a transgenic mouse wherein a targeting construct containing a transgene encoding the human B1 bradykinin receptor gene is inserted downstream of and operatively linked to the native mice bradykinin B1 promoter. This targeting construct also contains a fluxed neomycin resistance gene. The resulting transgenic animals are “humanized” for the bradykinin B1 receptor and are effectively on a null background for native, functional B1 receptor activity. These animals may be crossed with a Cre-deleter strain to generate transgenic offspring which absent of the floxed marker gene. The transgenic animals described herein provide for a model to The transgenic mice of the present invention provide for an animal model enabling the analysis of compounds that are selective for the human B1 bradykinin receptor, relative to the rodent (e.g., rat or mouse) B1 bradykinin receptor.
摘要翻译：产生非人转基因动物，例如转基因小鼠，其掺入缓激肽B1受体基因的非天然形式针对天然形式的缓激肽B1受体的无效表型。本发明的示例性部分公开了一种转基因小鼠，其中含有编码人B1缓激肽受体基因的转基因的靶向构建体插入天然小鼠缓激肽B1启动子的下游并与之有效连接。该靶向构建体还含有一种助溶的新霉素抗性基因。所得到的转基因动物对于缓激肽B1受体是“人源化的”，并且对于天然的功能性B1受体活性而言，其无效背景是有效的。这些动物可以与Cre-去除菌株杂交以产生不含斑点标记基因的转基因后代。本文所述的转基因动物提供了本发明的转基因小鼠相对于啮齿动物（例如大鼠或小鼠）B1缓激肽提供能够分析对人B1缓激肽受体有选择性的化合物的动物模型的模型受体。

12. 发明授权

US06555654B1 LDL-receptor 有权
标题翻译： LDL受体
公开(公告)号：US06555654B1
公开(公告)日：2003-04-29
申请号：US09402923
申请日：2000-02-14
申请人： John A. Todd , John W. Hess , Charles T. Caskey , Roger D Cox , David Gerhold , Holly Hammond , Patricia Hey , Yoshihiko Kawaguchi , Tony R. Merriman , Michael L. Metzker , Yusuke Nakagawa , Michael S. Phillips , Rebecca C. J. Twells
发明人： John A. Todd , John W. Hess , Charles T. Caskey , Roger D Cox , David Gerhold , Holly Hammond , Patricia Hey , Yoshihiko Kawaguchi , Tony R. Merriman , Michael L. Metzker , Yusuke Nakagawa , Michael S. Phillips , Rebecca C. J. Twells
IPC分类号： C07K1400
CPC分类号： C07K14/705 , A61K38/00 , A61K48/00
摘要： A novel receptor, “LDL-receptor related protein-3” (“LRP-3”), is provided, along with encoding nucleic acid. The gene is associated with type 1 diabetes (insulin dependent diabetes mellitus), and experimental evidence provides indication that it is the IDDM susceptibility gene IDDM4. In various aspects the invention provides nucleic acid, including coding sequences, oligonucleotide primers and probes, polypeptides, pharmaceutical compositions, methods of diagnosis or prognosis, and other methods relating to and based on the gene, including methods of treatment of diseases in which the gene may be implicated, including autoimmune diseases, such as glomerulonephritis, diseases and disorders involving disruption of endocytosis and/or antigen presentation, diseases and disorders involving cytokine clearance and/or inflammation, viral infection, elevation of free fatty acids or hypercholesterolemia, osteoporosis, Alzheimer's disease, and diabetes.
摘要翻译：提供了新的受体“LDL-受体相关蛋白-3”（“LRP-3”）以及编码核酸。该基因与1型糖尿病（胰岛素依赖性糖尿病）相关，实验证据表明其是IDDM易感基因IDDM4。在各个方面，本发明提供核酸，包括编码序列，寡核苷酸引物和探针，多肽，药物组合物，诊断或预后的方法，以及与该基因相关并基于该基因的其它方法，包括治疗其中基因可能涉及自身免疫性疾病，例如肾小球性肾炎，涉及细胞内吞和/或抗原呈递破坏的疾病和病症，涉及细胞因子清除和/或炎症的疾病和病症，病毒感染，游离脂肪酸升高或高胆固醇血症，骨质疏松症，阿尔茨海默病疾病和糖尿病。

13. 发明授权

US06281346B1 Rat ob-receptors and nucleotides encoding them 失效
标题翻译：大鼠ob受体和编码它们的核苷酸
公开(公告)号：US06281346B1
公开(公告)日：2001-08-28
申请号：US08803346
申请日：1997-02-20
申请人： John W. Hess , C. Thomas Caskey , Qingyun Liu , Michael Sean Phillips
发明人： John W. Hess , C. Thomas Caskey , Qingyun Liu , Michael Sean Phillips
IPC分类号： C12N1512
CPC分类号： C07K14/72
摘要： The rat ob receptor gene has been isolated and cloned. Two different alleles have been identified: the wild-type, and the fa-allele which differs from the wild type by only one base pair. The base pair change, however introduces an MspI restriction site into the DNA sequence, and also results in an amino acid change. Also part of the invention are the receptors, vectors containing the nucleic acid encoding the receptors, host cells transformed with this gene, and assays which use the gene or protein and identify new ligands.
摘要翻译：已经分离和克隆了大鼠ob受体基因。已经鉴定了两种不同的等位基因：野生型和fa型等位基因仅与一个碱基对不同于野生型。碱基对改变然后将MspI限制性位点引入DNA序列，并导致氨基酸变化。本发明的一部分还包括受体，含有编码受体的核酸的载体，用该基因转化的宿主细胞，以及使用该基因或蛋白质并鉴定新配体的测定法。

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