ADENOVIRUS-MEDIATED GENE DELIVERY INTO NEURONAL PRECURSORS OF THE ADULT-MOUSE BRAIN

Precursor cells found in the subventricular zone (SVZ) of the adult br ain can undergo cell division and migrate long distances before differ entiating into mature neurons. We have investigated the possibility of introducing genes stably into this population of cells. Replication-d efective adenoviruses were injected into the SVZ of the lateral ventri cle of adult mice. The adenoviruses carried a cDNA for the LacZ report er or the human p75 neurotrophin receptor, for which species-specific antibodies are available. Injection of the viruses into the SVZ led to efficient labeling of neuronal precursors. Two months after viral inj ection, infected cells were detected in the olfactory bulb, a signific ant distance from the site of injection. Labeled periglomerular and gr anular neurons with extensive dendritic arborization were found in the olfactory bulb. These results demonstrate that foreign genes can be e fficiently introduced into neuronal precursor cells. Furthermore, aden ovirus-directed infection can lead to long-term stable gene expression in progenitor cells found in the adult central nervous system.