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    ANIMAL MODEL OF CHOLINERGIC DYSFUNCTION TO EVALUATE COGNITIVE ENHANCERS AND DRUGS THAT IMPROVE MYASTHENIA
    3.
    发明申请
    ANIMAL MODEL OF CHOLINERGIC DYSFUNCTION TO EVALUATE COGNITIVE ENHANCERS AND DRUGS THAT IMPROVE MYASTHENIA 有权
    用于评估增强认知增强剂和改善MYASTHENIA的药物的胆碱功能的动物模型

    公开(公告)号：US20080052785A1

    公开(公告)日：2008-02-28

    申请号：US11842406

    申请日：2007-08-21

    申请人： Marc Caron ,  Vania Prado ,  Marco Prado ,  Raul Gainetdinov ,  Grace Pereira ,  Braulio Castro ,  Cristina Silva ,  Ivan Izquierdo

    发明人： Marc Caron ,  Vania Prado ,  Marco Prado ,  Raul Gainetdinov ,  Grace Pereira ,  Braulio Castro ,  Cristina Silva ,  Ivan Izquierdo

    IPC分类号： A01K67/027 ,  G01N33/00

    CPC分类号： C07K14/70571 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2217/20 ,  A01K2227/105 ,  A01K2267/0356 ,  C12N15/8509 ,  C12N2800/30

    摘要： Recombinant non-human mammals having reduced or no expression of vesicular acetylcholine transporter protein (VAChT) as compared to the corresponding wild-type mammal are provided. The mammal may have, e.g., impaired performance in object and social recognition and/or impaired neuromuscular performance and/or alterations in autonomic nervous system function as compared to the corresponding wild-type mammal. Methods of screening a compound for cholinergic activity or activity in treating a cholinergic neurotransmission disorder are also provided. In addition, a cell such as a nerve cell isolated from a mammal as described herein is provided, along with cell cultures, which are useful in vitro for screening the activity of candidate compounds for their effect on cholinergic neurotransmission, and for their activity in treating cholinergic neurotransmission disorders.

    摘要翻译： 提供了与相应的野生型哺乳动物相比具有减少或不表达水泡乙酰胆碱转运蛋白（VAChT）的重组非人哺乳动物。 与对应的野生型哺乳动物相比，哺乳动物可能具有例如对象和社会认知和/或受损的神经肌肉表现和/或自主神经系统功能的改变的性能受损。 还提供了筛选化合物胆碱能活性或治疗胆碱能神经传递障碍的活性的方法。 此外，提供了如本文所述的从哺乳动物分离的神经细胞的细胞以及细胞培养物，细胞培养物可用于体外筛选候选化合物对胆碱能神经传递的影响的活性，以及​​它们在治疗中的活性 胆碱能神经传递障碍。

    Mammals carrying functional single nucleotide polymorphisms in brain-specific tryptophan hydroxylase
    4.
    发明申请
    Mammals carrying functional single nucleotide polymorphisms in brain-specific tryptophan hydroxylase 失效
    在脑特异性色氨酸羟化酶中携带功能性单核苷酸多态性的哺乳动物

    公开(公告)号：US20080010692A1

    公开(公告)日：2008-01-10

    申请号：US11825202

    申请日：2007-07-05

    申请人： Marc Caron ,  Xiaodong Zhang ,  Martin Beaulieu ,  Raul Gainetdinov ,  Tatyana Sotnikova

    发明人： Marc Caron ,  Xiaodong Zhang ,  Martin Beaulieu ,  Raul Gainetdinov ,  Tatyana Sotnikova

    IPC分类号： G01N33/00 ,  A01K67/00 ,  C12N5/00

    CPC分类号： A01K67/0276 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0356 ,  C12N9/0071 ,  C12N15/8509 ,  C12N2800/30

    摘要： Recombinant or transgenic non-human mammals are described having a mutant tryptophan hydroxylase 2 (Tph2) gene resulting in altered synthesis of 5-hydroxytryptophan and serotonin in the brain. In some embodiments the mutant tryptophan hydroxylase 2 gene contains mouse R439H and/or P447R functional mutations, or their corresponding mutations in other species. Congenic non-human mammals having mutant tryptophan hydroxylase 2 genes are also provided. Methods of screening a compound for serotonergic activity or activity in treating a serotonergic neurotransmission dysregulation disorder are provided, which include administering a test compound to a recombinant non-human mammal and then detecting the presence or absence of serotonergic activity, or activity in treating a serotonergic neurotransmission dysregulation disorder, in the mammal. A cell such as a nerve cell (e.g., a central nervous system neuron) isolated from a transgenic or congenic mammal is also disclosed, along with cell cultures containing these cells. Such mammals and cells and cell cultures are useful in vitro for screening the activity of candidate compounds for their effect on serotonergic neurotransmission and for their activity in treating serotonergic neurotransmission dysregulation disorders.

    摘要翻译： 描述了具有突变色氨酸羟化酶2（Tph2）基因的重组或转基因非人哺乳动物，导致脑中5-羟色胺和5-羟色胺的合成改变。 在一些实施方案中，突变色氨酸羟化酶2基因含有小鼠R439H和/或P447R功能性突变或其他物种中相应的突变。 还提供了具有突变色氨酸羟化酶2基因的同种非人哺乳动物。 提供了筛选化合物用于治疗血清素能神经递质调节障碍的5-羟色胺能活性或活性的方法，其包括向重组非人哺乳动物施用测试化合物，然后检测血清素能活性的存在或不存在或治疗血清素能的活性 神经传递异常调节障碍。 还公开了从转基因或同基因哺乳动物分离的细胞例如分离自转基因或同种哺乳动物的神经细胞（例如中枢神经系统神经元）以及含有这些细胞的细胞培养物。 这样的哺乳动物和细胞和细胞培养物在体外可用于筛选候选化合物对5-羟色胺能神经传递的作用及其在治疗5-羟色胺能神经传递失调调节障碍中的活性。

    Antiparkinsonian Action of Phenylisopropylamines
    5.
    发明申请
    Antiparkinsonian Action of Phenylisopropylamines 有权
    苯基异丙胺的抗帕金森病作用

    公开(公告)号：US20070027208A1

    公开(公告)日：2007-02-01

    申请号：US11460046

    申请日：2006-07-26

    申请人： Marc Caron ,  Tatyana Sotnikova ,  Raul Gainetdinov

    发明人： Marc Caron ,  Tatyana Sotnikova ,  Raul Gainetdinov

    IPC分类号： A61K31/36 ,  A61K31/137

    CPC分类号： A61K31/137 ,  A61K31/198 ,  A61K31/36 ,  A61K31/55 ,  A61K45/06

    摘要： A method of treating a subject for Parkinson's disease comprises administering said subject a phenylisopropylamine in an amount effective to treat said Parkinson's disease. In some embodiments the method is used to treat at least a motor symptom of Parkinson's disease; in some embodiments the method is used to treat at least a non-motor symptom of Parkinson's disease.

    摘要翻译： 一种治疗受试者帕金森病的方法包括以有效治疗所述帕金森病的量给予所述受试者苯基异丙胺。 在一些实施方案中，该方法用于治疗帕金森病的至少一种运动症状; 在一些实施方案中，该方法用于治疗帕金森病的至少一种非运动性症状。

    Expression of G protein coupled receptors in yeast
    6.
    发明申请
    Expression of G protein coupled receptors in yeast 失效
    酵母中G蛋白偶联受体的表达

    公开(公告)号：US20050214739A1

    公开(公告)日：2005-09-29

    申请号：US10997069

    申请日：2004-11-23

    申请人： Klim King ,  Henrik Dohlman ,  Marc Caron ,  Robert Lefkowitz

    发明人： Klim King ,  Henrik Dohlman ,  Marc Caron ,  Robert Lefkowitz

    IPC分类号： C07K14/39 ,  C07K14/47 ,  C07K14/705 ,  C12N1/18 ,  C12N1/19 ,  C12N15/09 ,  C12N15/12 ,  C12N15/74 ,  C12N15/81 ,  C12P21/02 ,  C12Q1/00 ,  C12Q1/02 ,  C12Q1/68 ,  C12R1/865 ,  G01N33/566

    CPC分类号： G01N33/566 ,  C07K14/39 ,  C07K14/4722 ,  C07K14/70571 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/32 ,  C07K2319/61 ,  C07K2319/705 ,  C12N15/81 ,  C12Q1/6897 ,  G01N2333/726 ,  G01N2500/00

    摘要： Disclosed is a transformed yeast cell containing a first heterologous DNA sequence which codes for a mammalian G protein-coupled receptor and a second heterologous DNA sequence which codes for a mammalian G protein α subunit (mammalian Gα). The first and second heterologous DNA sequences are capable of expression in the cell, but the cell is incapable of expressing an endogenous G protein α-subunit (yeast Gα). The cells are useful for screening compounds which affect the rate of dissociation of Gα from Gβγ in a cell. Also disclosed is a novel DNA expression vector useful for making cells as described above. The vector contains a first segment comprising at least a fragment of the extreme amino-terminal coding sequence of a yeast G protein-coupled receptor. A second segment is positioned downstream from the first segment (and in correct reading frame therewith), with the second segment comprising a DNA sequence encoding a heterologous G protein-coupled receptor.

    摘要翻译： 公开了含有编码哺乳动物G蛋白偶联受体的第一异源DNA序列和编码哺乳动物G蛋白α亚基（哺乳动物细胞）的第二异源DNA序列的转化酵母细胞。 第一和第二异源DNA序列能够在细胞中表达，但是细胞不能表达内源性G蛋白α亚基（酵母Gαα）。 这些细胞可用于筛选化合物，这些化合物影响来自细胞中的β-氨基酸的解离速率。 还公开了用于如上所述制备细胞的新型DNA表达载体。 载体含有至少包含酵母G蛋白偶联受体的极端氨基末端编码序列的片段的第一片段。 第二片段位于第一片段的下游（并且在其正确的阅读框架中），第二片段包含编码异源G蛋白偶联受体的DNA序列。

    Modified G-protein coupled receptors
    7.
    发明申请
    Modified G-protein coupled receptors 有权
    修饰的G蛋白偶联受体

    公开(公告)号：US20050106623A1

    公开(公告)日：2005-05-19

    申请号：US11026435

    申请日：2004-12-30

    申请人： Robert Oakley ,  Lawrence Barak ,  Stephane Laporte ,  Marc Caron

    发明人： Robert Oakley ,  Lawrence Barak ,  Stephane Laporte ,  Marc Caron

    IPC分类号： C07K14/705 ,  C12Q1/68 ,  C07H21/04

    CPC分类号： C07K14/705

    摘要： The present invention relates to modified G-protein coupled receptors (GPCRs). The modified GPCRs of the present invention include GPCRs that have been modified to have carboxyl terminal tails comprising one or more sites of phosphorylation, preferably one or more clusters of phosphorylation sites. The modified GPCRs of the present invention may comprise a retained portion of a carboxyl-terminus region from a first GPCR fused to a polypeptide, wherein the polypeptide comprises the one or more clusters of phosphorylation. The present invention also relates to methods of screening compounds and sample solutions for GPCR activity using the modified GPCRS.

    摘要翻译： 本发明涉及修饰的G蛋白偶联受体（GPCR）。 本发明的修饰的GPCR包括已被修饰为具有包含一个或多个磷酸化位点的羧基末端尾，优选一个或多个磷酸化位点簇的GPCR。 本发明的修饰的GPCR可以包含与多肽融合的第一GPCR的羧基末端区域的保留部分，其中多肽包含一个或多个磷酸化簇。 本发明还涉及使用修饰的GPCRS筛选化合物和GPCR活性的样品溶液的方法。