Mice hemizygous for the transgenic insert are viable, normal in size, and do not display any behavioral abnormalities. Transgenic males are infertile. Proliferating cells that express the herpes simplex virus thymidine kinase (HSV-TK) transgene will metabolize ganciclovir (GCV) to toxic nucleotide analogues and undergo cell death. Transgene-derived HSV-TK is present exclusively in cells expressing endogenous Gfap. This coexpression occurs in brain astrocytes and adult neural stem cells, enteric glia, hepatic stellate cells, and unknown cells in heart, lung, kidney, adrenal, and spleen. Chronic GCV treatment for 21 days depletes GFAP-positive adult neural stem cells from forebrain proliferative zones. GCV treatment eliminated growth of primary multipotent neurospheres cultured from the germinal zones of postnatal and adult, but not early embryonic, transgenic mice. Notably, the same treatment prevented growth of secondary multipotent neurospheres from all three developmental stages. Stab or spinal cord injury with high dose GCV treatment for 7 days induces reactive astroctye cell death leading to altered leukocyte trafficking and impaired injury healing. High dose GCV treatment for 14 days ablates GFAP-positive glia from the jejunum and ileum leading to fulminant and fatal jejuno-ileitis. This mutant can be used instudies of adult neurogenesis, nervous system injury/repair mechanisms, and inflammatory bowel disease.
