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公开(公告)号：US06387656B1
公开(公告)日：2002-05-14
申请号：US09162524
申请日：1998-09-29
IPC分类号： C12D2106
CPC分类号： C07K14/47 , A01K2217/05
摘要： This invention provides an isolated nucleic acid molecule encoding a motor neuron restricted pattern, MNR2, protein. This invention provides an isolated nucleic acid molecule of at least 15 contiguous nucleotides capable of specifically hybridizing with a unique sequence included within the sequence of the nucleic acid molecule encoding a MNR2 protein. This invention provides a purified MNR2 protein, a polyclonal and monoclonal antibody directed to an epitope of an MNR2 protein. This invention provides a method of inducing differentiation somatic motor neurons which comprises expressing MNR2 protein in any neural progenitor cells. This invention provides a transgenic animal which expresses an MNR2 protein. This invention provides a pharmaceutical composition comprising a MNR2 protein and pharmaceutically acceptable carrier. This invention provides methods of treating subjects afflicted with an abnormality associated with a lack of normally functioning motor neurons, neurodegenerative disease, an acute nervous system injury and a neuromuscular disease which comprises contacting the subject with a pharmaceutical composition comprising a MNR2 protein and pharmaceutically acceptable carrier. This invention provides a functionally equivalent analog of MNR2 that induces or prevents MNR2 differentiation of neural progenitor cells.
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公开(公告)号：US07074771B2
公开(公告)日：2006-07-11
申请号：US10095932
申请日：2002-03-11
CPC分类号： C07K14/47 , A01K2217/05
摘要： This invention provides an isolated nucleic acid molecule encoding a motor neuron restricted pattern, MNR2, protein. This invention provides an isolated nucleic acid molecule of at least 15 contiguous nucleotides capable of specifically hybridizing with a unique sequence included within the sequence of the nucleic acid molecule encoding a MNR2 protein. This invention provides a purified MNR2 protein, a polyclonal and monoclonal antibody directed to an epitope of an MNR2 protein. This invention provides a method of inducing differentiation somatic motor neurons which comprises expressing MNR2 protein in any neural progenitor cells. This invention provides a transgenic animal which expresses an MNR2 protein. This invention provides a pharmaceutical composition comprising a MNR2 protein and pharmaceutically acceptable carrier. This invention provides methods of treating subjects afflicted with an abnormality associated with a lack of normally functioning motor neurons, neurodegenerative disease, an acute nervous system injury and a neuromuscular disease which comprises contacting the subject with a pharmaceutical composition comprising a MNR2 protein and pharmaceutically acceptable carrier. This invention provides a functionally equivalent analog of MNR2 that induces or prevents MNR2 differentiation of neural progenitor cells.
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公开(公告)号：US07192916B2
公开(公告)日：2007-03-20
申请号：US09820598
申请日：2001-03-29
IPC分类号： C07K14/00
CPC分类号： C07K14/47 , A01K2217/05
摘要： This invention provides isolated nucleic acids encoding a motor neuron restricted MNR2 protein, and a homeobox HB9 protein. Also provided are purified MNR2 and HB9 proteins, antibodies recognizing these proteins, transgenic animals expressing these proteins, and functionally equivalent analogs of these proteins. Finally, methods are disclosed for inducing differentiation of somatic motor neurons, and for treating diseases related to the lack of normally functioning motor neurons, neurodegenerative diseases, acute nervous system injury, and neuromuscular disease.
摘要翻译： 本发明提供编码运动神经元限制性MNR2蛋白的分离的核酸和同源框HB9蛋白。 还提供纯化的MNR2和HB9蛋白，识别这些蛋白的抗体，表达这些蛋白质的转基因动物和这些蛋白质的功能等同类似物。 最后，公开了用于诱导体细胞运动神经元的分化，以及用于治疗与缺乏正常运动神经元，神经变性疾病，急性神经系统损伤和神经肌肉疾病有关的疾病的方法。
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公开(公告)号：US09765297B2
公开(公告)日：2017-09-19
申请号：US12450830
申请日：2008-04-10
IPC分类号： C12Q1/02 , C12N5/079 , C12N5/0793
CPC分类号： C12N5/0619 , C12N2502/08 , C12N2506/02
摘要： The present invention relates to culture systems comprising differentiated stem cells, that may be used for identifying agents useful in treating degenerative nervous system disorders and are suitable for high-throughput screening applications. It is based, at least in part, on the discovery that co-cultures of (i) astrocytes expressing a mutated SODI gene and (ii) stem-cell derived motor neurons manifested cell death via a Bax-dependent mechanism, and modeled motor neuron death in amyotrophic lateral sclerosis.
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5.发明授权Homeodomain protein code specifying progenitor cell identify and neuronal fate in the ventral neural tube 失效同源二聚体蛋白质编码规定祖细胞鉴定和神经元命运在腹侧神经管中公开(公告)号：US06955802B1
公开(公告)日：2005-10-18
申请号：US09569259
申请日：2000-05-11
申请人： Thomas M. Jessell , James Briscoe , Johan Ericson
发明人： Thomas M. Jessell , James Briscoe , Johan Ericson
IPC分类号： A61K35/12 , A61K48/00 , C12N5/02 , C12N5/0797 , C12N15/867 , A61K49/00 , C12N5/00 , C12N5/08
CPC分类号： C12N15/86 , A61K35/12 , A61K48/00 , C12N5/0623 , C12N2501/41 , C12N2501/60 , C12N2510/00 , C12N2740/10043
摘要： Provided are genetically engineered cells comprising a neural stem cell and retroviral expression system in the neural stem cell, which is capable of expressing homeodomain transcription factor Nkx6.1 protein but does not express homeodomain transcription factor Irx3 protein or homeodomain transcription factor Nkx2.2 protein; which is capable of expressing homeodomain transcription factor Nkx6.1 protein and homeodomain transcription factor Irx3 protein; and which is capable of expressing homeodomain transcription factor Nkx2.2 protein or homeodomain transcription factor Nkx2.9 protein. Also provided are methods of generating such genetically engineered motor neurons, V2 neurons, and V3 neurons. Also provided are methods of treating subjects having a motor neuron injury or a motor neuron disease comprising implanting in injured/diseased neural tissue of the subject any of the provided genetically engineered cells, administering to such neural tissue retroviral expression systems which are capable of expressing the appropriate homeodomain protein(s), or transfecting neural stem cells with a retroviral vector, which is capable of expressing the required homeodomain transcription factor protein(s). Provided is a method of determining whether a chemical compound affects the generation of a motor neuron from a neural stem cell.
摘要翻译： 提供了在神经干细胞中包含神经干细胞和逆转录病毒表达系统的基因工程细胞，其能够表达同源结构域转录因子Nkx6.1蛋白，但不表达同源结构域转录因子Irx3蛋白或同源结构域转录因子Nkx2.2蛋白; 其能够表达同源结构域转录因子Nkx6.1蛋白和同源结构域转录因子Irx3蛋白; 并且能够表达同源结构域转录因子Nkx2.2蛋白或同源结构域转录因子Nkx2.9蛋白。 还提供了产生这种基因工程运动神经元，V2神经元和V3神经元的方法。 还提供了治疗具有运动神经元损伤或运动神经元疾病的受试者的方法，其包括在所提供的遗传工程细胞的受试者/患病神经组织中植入任何所提供的遗传工程改造的细胞，施用这样的神经组织逆转录病毒表达系统，其能够表达 适当的同源结构域蛋白，或用能够表达所需的同位素域转录因子蛋白的逆转录病毒载体转染神经干细胞。 提供一种确定化合物是否影响神经干细胞产生运动神经元的方法。
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公开(公告)号：US06379961B1
公开(公告)日：2002-04-30
申请号：US08717175
申请日：1996-09-20
IPC分类号： C12N506
CPC分类号： A61K38/1875 , A01K2227/40 , C07K14/51
摘要： This invention provides a composition comprising an amount of a purified protein selected from a group consisting of bone morphogenetic protein 4, bone morphogenetic protein, bone morphogenetic protein 7, dorsalin-1 and combinations thereof effective to stimulate neural crest cell differentiation and an acceptable carrier. This invention provides different uses of this composition.
摘要翻译： 本发明提供一种组合物，其包含一定量的选自骨形态发生蛋白4，骨形态发生蛋白，骨形态发生蛋白7，背风素-1及其有效刺激神经嵴细胞分化的组合的纯化蛋白质和可接受的载体。 本发明提供了该组合物的不同用途。
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7.发明授权
公开(公告)号：US5279966A
公开(公告)日：1994-01-18
申请号：US862021
申请日：1992-04-02
申请人： Thomas M. Jessell , Avihu Klar
发明人： Thomas M. Jessell , Avihu Klar
IPC分类号： C12N15/09 , A61K38/00 , C07K14/46 , C07K14/465 , C07K14/47 , C07K14/48 , C12N1/21 , C12N5/10 , C12P21/02 , C12N15/00 , C07H17/00 , C12N15/12
CPC分类号： C07K14/465 , C07K14/46 , C07K14/47 , C07K14/48 , A61K38/00
摘要： This invention provides an isolated vertebrate nucleic acid molecule encoding F-spondin. This invention also provides a probe comprising a nucleic acid molecule of at least 15 nucleotides capable of specifically hybridizing with a sequence included within the sequence of a nucleic acid molecule encoding a F-spondin. This invention provides a host vector system for the production of a F-spondin. This invention provides purified F-spondin and the uses of compositions containing purified F-spondin. This invention further provides a method of attaching nerve cells to a matrix using purified F-spondin. This invention also provides a method of stimulating nerve cell growth using purified F-spondin. This invention further provides a method of regenerating nerve call using purified F-spondin. Finally, this invention provides a pharmaceutical composition for stimulating nerve cell growth comprising an effective amount of purified F-spondin and a pharmaceutically acceptable carrier.
摘要翻译： 本发明提供了编码F-spondin的分离的脊椎动物核酸分子。 本发明还提供了一种包含至少15个核苷酸的核酸分子的探针，其能够与包含在编码F-脊椎动物的核酸分子的序列中的序列特异性杂交。 本发明提供了用于生产F-spondin的宿主载体系统。 本发明提供了纯化的F-spondin以及含有纯化F-spondin的组合物的用途。 本发明进一步提供了使用纯化的F-脊椎动物将神经细胞附着于基质的方法。 本发明还提供了使用纯化的F-spondin刺激神经细胞生长的方法。 本发明还提供了使用纯化的F-脊椎动物再生神经调节的方法。 最后，本发明提供了一种用于刺激神经细胞生长的药物组合物，其包含有效量的纯化的F-螺旋藻和药学上可接受的载体。
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8.发明授权DNA encoding serotonin 1C (5HT1c) receptor, isolated 5HT1c receptor, mammalian cells expressing same and uses thereof 失效编码5-羟色胺1C（5HT1c）受体的DNA，分离的5HT1c受体，表达其的哺乳动物细胞及其应用
公开(公告)号：US4985352A
公开(公告)日：1991-01-15
申请号：US298639
申请日：1989-01-18
申请人： David J. Julius , Richard Axel , Thomas M. Jessell
发明人： David J. Julius , Richard Axel , Thomas M. Jessell
IPC分类号： C07K14/705 , C07K16/28 , C12Q1/68
CPC分类号： C12Q1/6876 , C07K14/70571 , C07K16/28 , C12Q2600/158
摘要： The invention relates to DNA encoding a functional serotonin 5HT1c receptor, e.g., cDNA, and to the isolated, functional serotonin 5HT1c receptor encoded by such DNA. The invention also relates to mammalian cells expressing the cDNA encoding the 5HT1c receptor and to a DNA probe useful for detecting nucleic acid encoding the serotonin 5HT1c receptor. This invention provides methods for determining binding to the serotonin 5HT1c receptor, methods of detecting the expression, and the presence of the serotonin 5HT1c receptor on the surface of a cell and to a method of screening drugs to identify drugs which specifically interact with, and bind to the serotonin 5HT1c receptor on the surface of a cell.
摘要翻译： 本发明涉及编码功能性5-羟色胺5HT1c受体（例如cDNA）的DNA，以及由该DNA编码的分离的功能性5-羟色胺5HT1c受体。 本发明还涉及表达编码5HT1c受体的cDNA的哺乳动物细胞和可用于检测编码5-羟色胺5HT1c受体的核酸的DNA探针。 本发明提供了确定与5-羟色胺5HT1c受体的结合的方法，检测表达的方法和在细胞表面上存在的5-羟色胺5HT1c受体，以及筛选药物以鉴别与之特异性相互作用并结合的药物的方法 到细胞表面上的5-羟色胺5HT1c受体。
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9.发明授权Caudal motor neuron derived from embryonic stem cells under conditions essentially free of any retinoid 有权尾状运动神经元衍生自胚胎干细胞条件基本上没有任何类视黄醇公开(公告)号：US08969081B2
公开(公告)日：2015-03-03
申请号：US12653217
申请日：2009-12-09
申请人： Hynek Wichterle , Thomas M. Jessell , Mirza Peljto
发明人： Hynek Wichterle , Thomas M. Jessell , Mirza Peljto
IPC分类号： C12N5/02 , C12N5/0793 , C12N5/074 , C12N5/0735 , C12N5/0797 , A61K35/30
CPC分类号： C12N5/0619 , A61K35/30 , C12N5/0606 , C12N5/0623 , C12N5/0696 , C12N2501/115 , C12N2501/13 , C12N2501/155 , C12N2501/19 , C12N2501/385 , C12N2501/41 , C12N2506/02 , C12N2506/45
摘要： Disclosed are methods for generating a neuron expressing Hoxc8 transcription factor or a caudal motor neuron comprising culturing an embryonic stem cell in a composition which is essentially free of retinoids and comprises an isotonic salt solution, so as to generate the neuron which expresses Hoxc8 transcription factor or the caudal motor neuron. Disclosed are also methods for generating a caudal brachial motor neuron, a thoracic motor neuron, or a lumbar motor neuron from an embryonic stem cell in a composition essentially free of retinoids and comprising ADFNK medium, an amount of FGF-2, or Gdf11 respectively. Disclosed are also methods of transplanting a motor neuron into a subject comprising generating the motor neuron and transplanting the motor neuron into the subject. Disclosed is also a population of motor neuron cells enriched for motor neuron cells expressing Foxp1 and expressing a gene associated with Spinal Muscular Atrophy (SMA) or Amyotrophic Lateral Sclerosis (ALS).
摘要翻译： 公开了产生表达Hoxc8转录因子或尾部运动神经元的神经元的方法，包括在基本上不含类视黄醇的组合物中培养胚胎干细胞，并且包含等渗盐溶液，以产生表达Hoxc8转录因子的神经元或 尾部运动神经元。 还公开了在基本上不含类视黄醇的组合物中产生来自胚胎干细胞的尾部肱动脉神经元，胸部运动神经元或腰运动神经元的方法，并且分别包含一定量的FGF-2或Gdf11的ADFNK培养基。 还公开了将运动神经元移植到受试者中的方法，包括产生运动神经元并将运动神经元移植到受试者中。 还公开了富含表达Foxp1并表达与脊髓性肌萎缩（SMA）或肌萎缩性侧索硬化（ALS）相关的基因的运动神经元细胞的运动神经元细胞的群体。
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公开(公告)号：US5750502A
公开(公告)日：1998-05-12
申请号：US313288
申请日：1995-01-05
申请人： Thomas M. Jessell , Avihu Klar
发明人： Thomas M. Jessell , Avihu Klar
IPC分类号： C12N15/09 , A61K38/00 , C07K14/46 , C07K14/465 , C07K14/47 , C07K14/48 , C12N1/21 , C12N5/10 , C12P21/02 , A61K38/16
CPC分类号： C07K14/465 , C07K14/46 , C07K14/47 , C07K14/48 , A61K38/00
摘要： This invention provides an isolated vertebrate nucleic acid molecule encoding F-spondin. This invention also provides a probe comprising a nucleic acid molecule of at least 15 nucleotides capable of specifically hybridizing with a sequence included within the sequence of a nucleic acid molecule encoding an F-spondin. This invention further provides a method of attaching nerve cells to a matrix comprising contacting the matrix with nerve cells and purified F-spondin at a concentration effective to effect attachment of the cells to the matrix. This invention also provides a method of stimulating growth of a nerve cell comprising contacting the nerve cell with purified F-spondin at a concentration effective to stimulate growth of the nerve cell. This invention provides a method of regenerating nerve cells in a subject comprising administering to the subject purified F-spondin at a concentration effective to regenerate nerve cells in the subject. Finally, this invention provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and purified F-spondin.
摘要翻译： PCT No.PCT / US93 / 03164 Sec。 371 1995年1月5日第 102（e）日期1995年1月5日PCT提交1993年4月2日PCT公布。 公开号WO93 / 20196 日期：1993年10月14日本发明提供了编码F-spondin的分离的脊椎动物核酸分子。 本发明还提供了一种包含至少15个核苷酸的核酸分子的探针，其能够与包含在编码F-脊椎动物的核酸分子的序列中的序列特异性杂交。 本发明进一步提供了一种将神经细胞附着于基质的方法，包括使基质与神经细胞和纯化的F-spondin接触，其浓度有效地使细胞附着于基质。 本发明还提供一种刺激神经细胞生长的方法，其包括以有效刺激神经细胞生长的浓度使神经细胞与纯化的F-spondin接触。 本发明提供了一种在受试者中再生神经细胞的方法，其包括以有效再生受试者神经细胞的浓度给予受试者的纯化的F-脊椎动物。 最后，本发明提供了包含药学上可接受的载体和纯化的F-spondin的药物组合物。
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