公开(公告)号：US20040034882A1

公开(公告)日：2004-02-19

申请号：US10442797

申请日：2003-05-21

发明人： Wylie W. Vale ,  Tracy L. Bale ,  Kuo-Fen Lee ,  George W. Smith

IPC分类号： A01K067/027

CPC分类号： C07K14/723 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0356 ,  A61K38/00 ,  C07K14/503 ,  C12N15/8509

摘要： The present invention provides transgenic mice deficient in corticotropin releasing factor receptor 2 (CRFR2). Mice deficient for CRFR1 exhibit decreased anxiety-like behavior and a decreased stress response. In contrast, CRFR2 null mutant mice are hypersensitive to stress and display increased anxiety-like behavior. These mice are useful for the study of anxiety, depression, and the physiology of the HPA axis. CRFR2 null mutant mice also exhibit increased angiogenesis in all tissues examined. Thus, CRFR2 antagonists may be used to stimulate angiogenesis for the treatment of various conditions. In contrast, CRFR2 agonists may be used to inhibit angiogenesis. A combination of urocortin and bFGF was observed to stimulate rapid hair growth. The CRFR2 mutant mice are also useful for the study of the effects of CRFR2 deficiency on homeostatic responses to stress, including a high-fat diet, repeated cold stress, and glucose and insulin challenges. The mutant mice to such stresses enable methods to screen compounds for effects on homeostasis, which are useful in screening compounds to provide treatments for pathological conditions related to the regulation of homeostasis, including obesity and type 2 diabetes.

摘要翻译： 本发明提供了促肾上腺皮质激素释放因子受体2（CRFR2）缺陷的转基因小鼠。 CRFR1缺陷小鼠表现出焦虑状态的减轻和应激反应的降低。 相比之下，CRFR2无效突变体小鼠对应激过敏，并显示增加的焦虑样行为。 这些小鼠可用于研究焦虑，抑郁和HPA轴的生理学。 CRFR2无效突变小鼠在所有检查的组织中也表现出增加的血管发生。 因此，CRFR2拮抗剂可用于刺激血管生成用于治疗各种病症。 相比之下，CRFR2激动剂可用于抑制血管发生。 观察到尿皮质素和bFGF的组合刺激毛发快速生长。 CRFR2突变小鼠也可用于研究CRFR2缺乏对应激反应的稳态反应的影响，包括高脂肪饮食，重复冷应激和葡萄糖和胰岛素挑战。 对这种应激的突变小鼠使筛选化合物的方法能够影响体内平衡，其可用于筛选化合物以提供与稳态调节（包括肥胖症和2型糖尿病）相关的病理状况的治疗。

公开(公告)号：US20030186284A1

公开(公告)日：2003-10-02

申请号：US10333786

申请日：2003-01-24

发明人： Masaharu Noda ,  Akihiro Fujikawa

IPC分类号： G01N033/00 ,  C12Q001/68

CPC分类号： C12N15/8509 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0356 ,  A01K2267/0368 ,  A01K2267/0393 ,  C12N9/16 ,  C12Q1/42 ,  G01N33/5088 ,  G01N33/68 ,  G01N2333/205

摘要： An object of the present invention is to provide a remedy for dysfunction of central monoamine pathway, a method for screening a PTPnull inhibitor or activator, which is useful as a remedy for gastric ulcer caused by Helicobacter pylori or pleiotrophin which is a heparin-binding secretory protein, and a non-human model animal being hyposensitive to a stimulant drug, VacA which is a toxin of Helicobacter pylori, or pleiotrophin by utilizing the physiological function of PTPnull. After administering a subject material to PTPnull knockout mice and wild-type mice, PTPnull activity in the PTPnull knockout mice and the wild-type mice is compared and evaluated to screen a PTPnull inhibitor or activator. Examples of the comparison and the evaluation of the PTPnull activity include the comparison and the evaluation of the function of central monoamine pathway such as changes in the level of central monoamine metabolism, sensitivity to a stimulant drug, the presence of dysfunction of mesolimbic dopamine pathway, level of acclimation to new circumstances, or stress-responsiveness, and the comparison and the evaluation of the level of binding to VacA, a toxin of Helicobacter pylori, or pleiotrophin.

摘要翻译： 本发明的目的是提供一种中枢单胺途径功能障碍的补救方法，一种筛选PTPzeta抑制剂或活化剂的方法，该方法可用作由幽门螺旋杆菌或多潜养蛋白引起的胃溃疡的治疗药物，其为肝素结合分泌物 蛋白质和对刺激性药物VacA（其是幽门螺杆菌毒素）的VacA或通过利用PTPzeta的生理功能的多余营养素不敏感的非人类模型动物。 对PTPzeta敲除小鼠和野生型小鼠施用主题材料后，比较PTPzeta敲除小鼠和野生型小鼠中的PTPzeta活性，并筛选PTPzeta抑制剂或活化剂。 比较和评估PTPzeta活性的实例包括中枢单胺途径的功能的比较和评价，例如中枢单胺代谢水平的变化，对兴奋剂药物的敏感性，中脑内膜多巴胺途径的功能障碍的存在， 适应新情况或压力反应的水平，以及与幽门螺杆菌或多柔比星毒素VacA的结合水平的比较和评估。

公开(公告)号：US20030167495A1

公开(公告)日：2003-09-04

申请号：US10141541

申请日：2002-05-07

发明人： Stefan M. Pulst

IPC分类号： A01K067/027

CPC分类号： C12N15/8509 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0356 ,  A01K2267/0362 ,  C12N2517/02 ,  C12Q1/6883

摘要： The invention provides a mutant non-human mammal having a disrupted SCA2 gene, in particular, a mutant mouse having a disrupted SCA2 gene. The invention also provides methods of identifying a therapeutic agent for use in treating obesity or memory impairment by administering a compound to the mutant non-human mammal having a disrupted SCA2 gene and screening said mutant non-human mammal for reduced obesity, thereby identifying a therapeutic agent for use in treating obesity.

摘要翻译： 本发明提供具有破坏的SCA2基因的突变非人哺乳动物，特别是具有破坏的SCA2基因的突变小鼠。 本发明还提供了通过向具有破坏的SCA2基因的突变非人哺乳动物施用化合物来鉴定用于治疗肥胖或记忆障碍的治疗剂的方法，并筛选所述突变非人哺乳动物以减少肥胖，由此鉴定治疗 用于治疗肥胖症的药剂。

公开(公告)号：US20030106073A1

公开(公告)日：2003-06-05

申请号：US10026937

申请日：2001-12-21

发明人： Keith D. Allen ,  Mark Moore ,  William Matthews

IPC分类号： A01K067/027 ,  A61K031/00 ,  C12N005/06

CPC分类号： A01K67/0276 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0356 ,  A01K2267/0393 ,  A61K38/00 ,  C07K14/70571 ,  C12N15/8509 ,  C12N2800/30

摘要： The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising mutations in an FPR-RS 4 gene. Such transgenic mice are useful as models for disease and for identifying agents that modulate gene expression and gene function, and as potential treatments for various disease states and disease conditions.

摘要翻译： 本发明涉及转基因动物，以及与基因功能表征相关的组合物和方法。 具体地说，本发明提供了包含FPR-RS4基因突变的转基因小鼠。 这样的转基因小鼠可用作疾病的模型并用于鉴定调节基因表达和基因功能的试剂，以及作为各种疾病状态和疾病状况的潜在治疗。

公开(公告)号：US20030093825A1

公开(公告)日：2003-05-15

申请号：US10180946

申请日：2002-06-25

发明人： Keith D. Allen

IPC分类号： A01K067/027 ,  C12N005/06

CPC分类号： A01K67/0276 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0356 ,  A01K2267/0393 ,  C07K14/70571 ,  C12N15/8509 ,  C12N2800/30

摘要： The present invention relates to compositions and methods relating to the characterization and function of PNR. Specifically, the present invention provides transgenic animals comprising disruptions in a PNR gene and methods of treating diseases conditions, such as schizophrenia. The present invention further relates to agents that modulate PNR and methods of screening for agents that modulate PNR for the treatment of diseases and conditions such as schizophrenia.

摘要翻译： 本发明涉及与PNR的表征和功能相关的组合物和方法。 具体地说，本发明提供包含PNR基因中断的转基因动物以及治疗诸如精神分裂症等疾病的方法。 本发明还涉及调节PNR的试剂和筛选调节PNR以用于治疗疾病和病症例如精神分裂症的药剂的方法。

公开(公告)号：US20030056236A1

公开(公告)日：2003-03-20

申请号：US10225835

申请日：2002-08-22

发明人： Peter Ronald Maycox ,  Charles Alan Reavill

IPC分类号： A01K067/027 ,  C12N005/06

CPC分类号： C12N15/907 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0306 ,  A01K2267/0356 ,  C07K14/705 ,  C12N15/8509 ,  C12N2840/203 ,  G01N33/5088 ,  G01N2333/46 ,  G01N2800/52

摘要： The present invention provides a transgenic non-human animal and method for using the same in evaluating a therapeutic agent for use in the treatment of Schizophrenia. More specifically, the invention is directed to a transgenic non-human animal which is incapable of expressing functional EDG2 protein. A theraupeutic agent is administered to the transgenic non-human animal incapable of expressing functional EDG2 protein and the effect of the agent on the animal is evaluated.

摘要翻译： 本发明提供了一种转基因非人动物及其用于评价用于治疗精神分裂症的治疗剂的方法。 更具体地，本发明涉及不能表达功能性EDG2蛋白的转基因非人动物。 向不能表达功能性EDG2蛋白质的转基因非人动物施用麻黄碱剂，并评估该药物对动物的作用。

公开(公告)号：US20030056232A1

公开(公告)日：2003-03-20

申请号：US10130254

申请日：2002-09-06

发明人： Hiroyuki Nawa ,  Takashi Futamura

IPC分类号： A01K067/00 ,  A61K038/18

CPC分类号： C12N15/8509 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0356 ,  C07K14/485

摘要： To provide a an animal with schizophrenic sensorimotor and behavioral abnormalities, a specific protein factor inhibiting development of brain function is administrated to a juvenile animal in the stage of its development and an animal exhibiting sensorimotor and behavioral abnormalities is prepared. As the sensorimotor and behavioral abnormalities observed in the animal of the present invention is very similar to schizophrenia, the animal is useful for development of an anti-schizophrenic medicine and a diagnostic agent for schizophrenia.

摘要翻译： 为了给动物提供精神分裂症感觉运动和行为异常，在其发育阶段向少年动物施用抑制脑功能发展的特定蛋白因子，并制备出具有感觉运动和行为异常的动物。 由于在本发明的动物中观察到的感觉运动和行为异常与精神分裂症非常相似，所以该动物可用于开发抗精神分裂症药物和用于精神分裂症的诊断剂。

公开(公告)号：US20030051268A1

公开(公告)日：2003-03-13

申请号：US10179410

申请日：2002-06-24

发明人： Keith D. Allen

IPC分类号： A01K067/027

CPC分类号： A01K67/0276 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0356 ,  A01K2267/0393 ,  A61K38/00 ,  C07K14/705 ,  C12N15/8509 ,  C12N2800/30

摘要： The present invention relates to compositions and methods relating to the characterization and function of CYT28. Specifically, the present invention provides transgenic animals comprising disruptions in a CYT28 gene and methods of treating diseases conditions, such as pain. The present invention further relates to agents that modulate CYT28 and methods of screening for agents that modulate CYT28 for the treatment of diseases and conditions such as pain.

摘要翻译： 本发明涉及与CYT28的表征和功能相关的组合物和方法。 具体地，本发明提供了包含CYT28基因中断的转基因动物以及治疗诸如疼痛等疾病疾病的方法。 本发明还涉及调节CYT28的药剂和筛选调节CYT28用于治疗疾病和病症如疼痛的药剂的方法。

公开(公告)号：US20030017479A1

公开(公告)日：2003-01-23

申请号：US10014079

申请日：2001-12-11

发明人： Joshua M. Kaplan ,  Allison J. Oppenheimer ,  Anne C. Hart

IPC分类号： C12Q001/68 ,  A61K031/00

CPC分类号： G01N33/5058 ,  A01K67/0336 ,  A01K2217/05 ,  A01K2227/703 ,  A01K2267/0356 ,  A61K49/0008 ,  C07K14/43545 ,  C07K14/4722 ,  C12N9/88 ,  C12N2830/008 ,  C12Q1/6897 ,  G01N33/5008 ,  G01N33/502 ,  G01N33/5023 ,  G01N33/6896 ,  G01N2333/43534 ,  G01N2800/28

摘要： In general, the invention provides methods for identifying genes involved in neurodegeneration and therapeutics for treating animals with a neurodegenerative disease. Methods and kits for the detection of compounds which enhance neuroprotection and diagnostic kits for the detection of neurodegenerative diseases are also a part of the invention.

摘要翻译： 通常，本发明提供用于鉴定参与神经变性的基因和治疗用于治疗具有神经变性疾病的动物的方法。 用于检测增强神经保护性的化合物和用于检测神经变性疾病的诊断试剂盒的方法和试剂盒也是本发明的一部分。

公开(公告)号：US20030014772A1

公开(公告)日：2003-01-16

申请号：US10112286

申请日：2002-03-28

发明人： Keith D. Allen

IPC分类号： A01K067/027 ,  C12N005/06

CPC分类号： A01K67/0276 ,  A01K2217/072 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0356 ,  A01K2267/0393 ,  C12N9/1205 ,  C12N15/8509 ,  C12N2800/30

摘要： The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising mutations in a MSK2 gene. Such transgenic mice are useful as models for disease and for identifying agents that modulate gene expression and gene function, and as potential treatments for various disease states and disease conditions.

摘要翻译： 本发明涉及转基因动物，以及与基因功能表征相关的组合物和方法。 具体地，本发明提供包含MSK2基因突变的转基因小鼠。 这样的转基因小鼠可用作疾病的模型并用于鉴定调节基因表达和基因功能的试剂，以及作为各种疾病状态和疾病状况的潜在治疗。