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Role of alpha1-adrenergic receptors

机译:α1-肾上腺素受体的作用

摘要

The present invention is directed to a transgenic non-human mammal (e.g., a rodent such as a mouse) whose genome comprises a recombinant nucleic acid sequence comprising an α1A-adrenergic receptor (AR) and a marker peptide (e.g., a fluorescent peptide such as green fluorescent protein and an enhanced green fluorescent protein) operably linked to all or a functional portion of an α1A-AR promoter, wherein the α1A-AR (e.g., human α1A-AR) and the marker peptide are expressed as a fusion protein in the transgenic non-human mammal. The present invention also provides methods of producing a transgenic non-human mammal whose genome comprises a recombinant nucleic acid sequence comprising an α1A-AR and a marker peptide, as well as targeting constructs for use in such methods. The invention also provides a source of cells (for example, tissue, cells, cellular extracts, organelles) and animals useful for elucidating the function of α1A-AR in intact animals. Further aspects of the invention provide methods for the identification of agents that modulate neural stem cell or progenitor cell differentiation by α1A-AR; methods of determining whether a cell is a neural stem cell; methods of regulating differentiation or proliferation of a neural stem cell or progenitor cell; and methods of treating neurodegenerative diseases, cognitive impairment or conditions.
机译:本发明涉及转基因非人类哺乳动物(例如,啮齿动物,例如小鼠),其基因组包含重组核酸序列,该重组核酸序列包含α 1A -肾上腺素能受体(AR)和标志物与α 1A -AR启动子的全部或功能部分可操纵地连接的肽(例如,诸如绿色荧光蛋白和增强的绿色荧光蛋白之类的荧光肽),其中α 1A < / Sub> -AR(例如人α 1A -AR)和标志物肽在转基因非人哺乳动物中表达为融合蛋白。本发明还提供了生产转基因非人类哺乳动物的方法,该基因组包含包含α 1A -AR和标志物肽的重组核酸序列,以及用于此类方法的靶向构建体。本发明还提供了细胞来源(例如组织,细胞,细胞提取物,细胞器)和动物源,可用于阐明完整动物中α 1A -AR的功能。本发明的另一方面提供了鉴定通过α 1A -AR调节神经干细胞或祖细胞分化的药物的方法。确定细胞是否为神经干细胞的方法;调节神经干细胞或祖细胞分化或增殖的方法;和治疗神经退行性疾病,认知障碍或状况的方法。

著录项

  • 公开/公告号US2008301822A1

    专利类型

  • 公开/公告日2008-12-04

    原文格式PDF

  • 申请/专利权人 DIANNE M. PEREZ;

    申请/专利号US20080151594

  • 发明设计人 DIANNE M. PEREZ;

    申请日2008-05-07

  • 分类号A01K67/027;C12N15/09;C07H21/04;C12N5/06;G01N33/53;

  • 国家 US

  • 入库时间 2022-08-21 19:30:29

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