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 a<SUB>1A</SUB>-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 a<SUB>1A</SUB>-AR promoter, wherein the a<SUB>1A</SUB>-AR (e.g., human a<SUB>1A</SUB>-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 a<SUB>1A</SUB>- 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 a<SUB>1A</SUB>-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 a<SUB>1A</SUB>-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. |