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1. 发明授权

US06927317B2 Modulating ramp activity 失效
标题翻译：调整斜坡活动
公开(公告)号：US06927317B2
公开(公告)日：2005-08-09
申请号：US10006542
申请日：2001-11-30
申请人： John D. McNeish , Walter C. Soeller , John F. Thompson
发明人： John D. McNeish , Walter C. Soeller , John F. Thompson
IPC分类号： A01K67/027 , A61K38/00 , A61K45/00 , A61K49/00 , A61P1/16 , A61P3/08 , A61P9/04 , A61P9/10 , A61P9/12 , A61P15/00 , A61P17/00 , A61P21/00 , A61P25/16 , A61P25/18 , A61P25/22 , A61P25/24 , A61P25/28 , A61P43/00 , C07K14/705 , C12N5/08 , C12N5/10 , C12N15/09 , C12N15/85 , C12Q1/02 , C12N5/00 , C12N5/02
CPC分类号： C12N15/8509 , A01K67/0276 , A01K2217/072 , A01K2217/075 , A01K2227/105 , A01K2267/03 , A01K2267/0375 , A61K38/00 , A61K49/0004 , C07K14/705 , C12N2503/02 , C12N2510/00 , C12N2517/02 , C12N2800/30 , C12N2830/008 , C12N2830/85 , C12N2840/203
摘要： The invention provides genetically-modified non-human mammals and genetically-modified animal cells containing a disrupted RAMP1, RAMP2, or RAMP3 gene. Also provided by the invention are methods of screening for agents that modulate the activity or expression of a RAMP and methods of treating mammals to modulate liver function and/or muscle metabolism.
摘要翻译：本发明提供遗传修饰的非人哺乳动物和含有破坏的RAMP1，RAMP2或RAMP3基因的遗传修饰的动物细胞。本发明还提供筛选调节RAMP的活性或表达的试剂的方法以及治疗哺乳动物调节肝功能和/或肌肉代谢的方法。

2. 发明授权

US06693226B1 Transgenic mice expressing human p25 失效
标题翻译：表达人p25的转基因小鼠
公开(公告)号：US06693226B1
公开(公告)日：2004-02-17
申请号：US09496445
申请日：2000-02-02
申请人： John D. McNeish , Michael K. Ahlijanian
发明人： John D. McNeish , Michael K. Ahlijanian
IPC分类号： A01K6700
CPC分类号： A01K67/0275 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/105 , A01K2267/0312 , A01K2267/0318 , C07K14/4738 , C12N15/8509 , C12N2830/008
摘要： The invention provides transgenic, non-human animals and transgenic non-human mammalian cells harboring a transgene encoding a p25 (activator of the protein kinase cdk 5) polypeptide. The two neuropathological lesions associated with Alzheimer's disease (AD) are amyloid plaques and neurofibrillary tangles (NFTs), composed predominantly of amyloid &bgr; peptides and hyperphosphorylated tau, respectvely. While animal models for plaque formation exist, there is no animal model that recapitulates the formation of NFTs. This invention provides transgenic mice that overexpress human p25, an activator of cdk5, resulting in tau that is hyperphosphorylated at AD-relevant epitopes. Deposition of tau is detected in the amygdala, thalamus and cortex. Increased phosphorylated neurofilament, silver-positive neurons and neuronal death are also observed in these regions. We conclude that the overexpression of p25, an activator of cdk5, is sufficient to produce hyperphosphorylation of tau and neuronal death. The p25 transgenic mouse represents the first model for tau pathology in AD.
摘要翻译：本发明提供具有编码p25（蛋白激酶cdk 5的活化剂）多肽的转基因的转基因非人动物和转基因非人哺乳动物细胞。与阿尔茨海默病（AD）相关的两种神经病理学病变是淀粉样斑块和神经原纤维缠结（NFTs），主要由淀粉样β肽组成，超磷酸化tau。虽然存在斑块形成的动物模型，但没有重现NFT形成的动物模型。本发明提供过表达人p25的转基因小鼠，其是cdk5的激活剂，导致在AD相关表位处被过度磷酸化的tau。在杏仁核，丘脑和皮质中检测到tau的沉积。在这些区域也观察到增加的磷酸化神经丝，银阳性神经元和神经元死亡。我们得出结论，cd25的激活剂p25的过度表达足以产生tau和神经元死亡的高度磷酸化。 p25转基因小鼠代表AD中tau病理学的第一个模型。

3. 发明申请

US20080282364A1 Phosphodiesterase 9 Inhibition as Treatment for Obesity-Related Conditions 审中-公开
标题翻译：磷酸二酯酶9抑制作为肥胖相关条件的治疗
公开(公告)号：US20080282364A1
公开(公告)日：2008-11-13
申请号：US10577700
申请日：2004-10-18
申请人： Shawn C Black , Earl M Gibbs , John D McNeish
发明人： Shawn C Black , Earl M Gibbs , John D McNeish
IPC分类号： A01K67/027 , C12N5/10 , C12N15/85
CPC分类号： C12N15/8509 , A01K2217/075 , A01K2227/105 , A01K2267/0306 , A01K2267/0393 , A61K31/437 , A61K31/505 , A61K31/519
摘要： The present invention is directed to methods to decrease body weight and/or body fat in an animal, e.g., in the treatment of overweight or obese patients (e.g., humans or companion animals), or as a means to produce leaner meat in food stock animals (e.g., cattle, chickens, pigs), and methods to treat eating disorders (e.g., binge eating disorder and bulimia) in patients in need thereof by administering a PDE9 inhibitor. The invention also features biological tools to further study PDE9 function, i.e., genetically-modified mice and animal cells having a PDE9 gene disruption.
摘要翻译：本发明涉及减少动物体重和/或身体脂肪的方法，例如在超重或肥胖患者（例如，人或伴侣动物）的治疗中，或作为在食品中生产瘦肉的方法动物（例如牛，鸡，猪）以及通过施用PDE9抑制剂来治疗有需要的患者的进食障碍（例如暴饮暴食和贪食症）的方法。本发明还具有用于进一步研究PDE9功能的生物学工具，即具有PDE9基因破坏的遗传修饰的小鼠和动物细胞。

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