公开(公告)号：US20060230466A1

公开(公告)日：2006-10-12

申请号：US11449216

申请日：2006-06-07

申请人： Karl Weisgraber ,  Robert Farese ,  Robert Raffai ,  Li-Ming Dong

发明人： Karl Weisgraber ,  Robert Farese ,  Robert Raffai ,  Li-Ming Dong

IPC分类号： A01K67/027 ,  C12N5/06

CPC分类号： C12N15/8509 ,  A01K67/0276 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2217/072 ,  A01K2227/105 ,  A01K2267/0312 ,  A01K2267/0356 ,  A01K2267/0362 ,  A01K2267/0375 ,  C07K14/775 ,  C12N2517/02 ,  C12N2800/30 ,  G01N33/6896 ,  G01N33/92 ,  G01N2500/10 ,  G01N2800/044

摘要： The invention provides gene-targeted non-human animals comprising a genetically modified apoE gene encodes a recombinant apoE polypeptide displaying domain interaction. The invention further provides cells isolated from the gene-targeted animals, which cells produce a recombinant apoE polypeptide displaying domain interaction. The invention further provides methods of identifying agents that reduce apoE4 domain interaction, and which are useful to treat apoE4-related neurological and cardiovascular disorders.

公开(公告)号：US20080075663A1

公开(公告)日：2008-03-27

申请号：US11765408

申请日：2007-06-19

申请人： Robert Raffai ,  Karl Weisgraber

发明人： Robert Raffai ,  Karl Weisgraber

IPC分类号： A01K67/00 ,  A61K49/00

CPC分类号： A61K49/0008 ,  A01K67/0275 ,  A01K67/0276 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0362 ,  A01K2267/0375 ,  C07K14/705 ,  C07K14/775 ,  C12N15/8509 ,  C12N2800/30

摘要： An animal model has been developed where the animals can survive myocardial infarctions caused by diet-induced coronary atherosclerosis, and live with chronic heart failure. This animal model is a result of reduced activity of scavenger receptor class BI (SR-BI) and ApoE and the inducible activity of the Mx1-Cre gene. In a preferred embodiment, the model is a result of crossbreeding two transgenic mouse lines: a knockout of SR-BI (SRBI−/−) and an impaired ApoE expressor (Apoeh/h) to generate a strain referred to as Apoeh/hSRB1−/− mice, which is then crossbred to mice that carry the inducible Mx1-Cre transgene. The Apoeh/hSRB1−/− mouse model is genetically modified, enabling the offspring to rapidly and permanently lower their high blood cholesterol levels caused by dietary challenge. The ability to rapidly and permanently lower blood cholesterol levels in these mice stops and may cause the regression of occlusive coronary atherosclerosis restoring blood flow to the heart, allowing the mice to survive from myocardial infarction and live with chronic heart failure.

摘要翻译： 已经开发了一种动物模型，其中动物可以存活由饮食诱发的冠状动脉粥样硬化引起的心肌梗死，并且伴有慢性心力衰竭。 该动物模型是清道夫受体类BI（SR-BI）和ApoE的活性降低以及Mx1-Cre基因的诱导活性的结果。 在优选的实施方案中，该模型是杂交两个转基因小鼠品系的结果：SR-BI（SRBI - / - ）的敲除和受损的ApoE表达（Apoe / SUP>）以产生称为Apoe小鼠的菌株，然后与携带可诱导Mx1-Cre转基因的小鼠杂交。 Apoe小鼠模型是基因修饰的，使得后代能够快速且永久地降低由饮食挑战引起的高血胆固醇水平。 快速和永久降低这些小鼠血液胆固醇水平的能力停止，并且可能导致闭塞性冠状动脉粥样硬化的消退，恢复心脏的血流量，使小鼠能够从心肌梗死中存活并与慢性心力衰竭一起生存。

公开(公告)号：US20060073104A1

公开(公告)日：2006-04-06

申请号：US11244268

申请日：2005-10-04

申请人： Robert Mahley ,  Karl Weisgraber ,  Yadong Huang

发明人： Robert Mahley ,  Karl Weisgraber ,  Yadong Huang

IPC分类号： A61L9/04 ,  A61K31/655 ,  A61K31/5377 ,  A61K31/496 ,  A61K31/423 ,  A61K31/381 ,  A61K31/185

CPC分类号： A61K31/185 ,  A61K31/381 ,  A61K31/423 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/655

摘要： The present invention provides compounds that inhibit apoE4 domain interaction; and compositions, including pharmaceutical compositions, comprising the compounds. The present invention provides methods of treating apoE4-related disorders. The methods generally involve administering to an individual in need thereof a therapeutically effective amount of an apoE4 domain interaction inhibitor.

摘要翻译： 本发明提供抑制apoE4结构域相互作用的化合物; 和包含该化合物的组合物，包括药物组合物。 本发明提供了治疗apoE4相关疾病的方法。 所述方法通常涉及向有需要的个体施用治疗有效量的apoE4结构域相互作用抑制剂。

公开(公告)号：US07960606B2

公开(公告)日：2011-06-14

申请号：US11765408

申请日：2007-06-19

申请人： Robert L. Raffai ,  Karl Weisgraber

发明人： Robert L. Raffai ,  Karl Weisgraber

IPC分类号： A01K67/00 ,  A01K67/027 ,  C12N15/00 ,  G01N33/00

CPC分类号： A61K49/0008 ,  A01K67/0275 ,  A01K67/0276 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0362 ,  A01K2267/0375 ,  C07K14/705 ,  C07K14/775 ,  C12N15/8509 ,  C12N2800/30

摘要： An animal model has been developed where the animals can survive myocardial infarctions caused by diet-induced coronary atherosclerosis, and live with chronic heart failure. This animal model is a result of reduced activity of scavenger receptor class BI (SR-BI) and ApoE and the inducible activity of the Mx1-Cre gene. In a preferred embodiment, the model is a result of crossbreeding two transgenic mouse lines: a knockout of SR-BI (SRBI−/−) and an impaired ApoE expressor (Apoeh/h) to generate a strain referred to as Apoeh/hSRB1−/− mice, which is then crossbred to mice that carry the inducible Mx1-Cre transgene. The Apoeh/hSRB1−/− mouse model is genetically modified, enabling the offspring to rapidly and permanently lower their high blood cholesterol levels caused by dietary challenge. The ability to rapidly and permanently lower blood cholesterol levels in these mice stops and may cause the regression of occlusive coronary atherosclerosis restoring blood flow to the heart, allowing the mice to survive from myocardial infarction and live with chronic heart failure.

摘要翻译： 已经开发了一种动物模型，其中动物可以存活由饮食诱发的冠状动脉粥样硬化引起的心肌梗死，并且伴有慢性心力衰竭。 该动物模型是清道夫受体类BI（SR-BI）和ApoE的活性降低以及Mx1-Cre基因的诱导活性的结果。 在优选的实施方案中，该模型是杂交两种转基因小鼠品系的结果：SR-BI（SRBI - / - ）的敲除和受损的ApoE表达（Apoeh / h）以产生称为Apoeh / hSRB1- / - 小鼠，然后与携带诱导型Mx1-Cre转基因的小鼠杂交。 Apoeh / hSRB1 - / - 小鼠模型是基因修饰的，使后代可以快速，永久地降低由饮食挑战引起的高血胆固醇水平。 快速和永久降低这些小鼠血液胆固醇水平的能力停止，并且可能导致闭塞性冠状动脉粥样硬化的消退，恢复心脏的血流量，使小鼠能够从心肌梗死中存活并与慢性心力衰竭一起生存。