| 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 alpha1A-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 alpha1A-AR promoter, wherein the alpha1A-AR (e.g., human alpha1A-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 alpha1A-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 alpha1A-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 alpha1A-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.
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