Adeno-associated virus effectively mediates conditional gene modification in the brain

• DOI: 10.1073/pnas.042678699
• Publication Date: 2002-07-26T14:37:36Z
• Authors: Brian K. Kaspar; Bryce Vissel; Tasha Bengoechea; Steven Crone; Lynne Randolph-Moore; Rolf Muller; Eugene P. Brandon; David Schaffer; Inder M. Verma; Kuo-Fen Lee; Stephen F. Heinemann; Fred H. Gage
• Keywords: Recombination, Genetic; 0303 health sciences; Integrases; Recombinant Fusion Proteins; Genetic Vectors; Green Fluorescent Proteins; Homozygote; Gene Transfer Techniques; Brain; Mice, Transgenic; Dependovirus; Hippocampus; Immunohistochemistry; Corpus Striatum; Recombinant Proteins; Cell Line; 3. Good health; Luminescent Proteins; Mice; 03 medical and health sciences; Animals; Humans; Septum of Brain

The Cre/ lox P system is increasingly showing promise for investigating genes involved in neural function. Here, we demonstrate that in vivo modification of genes in the mouse brain can be accomplished in a spatial- and temporal-specific manner by targeted delivery of an adeno-associated virus (AAV) encoding a green fluorescent protein/Cre recombinase (GFP/Cre) fusion protein. By using a reporter mouse, in which Cre recombinase activates β-galactosidase expression, we demonstrate long-term recombination of neurons in the hippocampus, striatum, and septum as early as 7 days after stereotaxic injection of virus. Recombined cells were observed for at least 6 months postinjection without evidence of cell loss or neural damage. AAV-mediated delivery of GFP/Cre provides a valuable approach to alter the mouse genome, as AAV delivers genes efficiently to neurons with low toxicity. This approach will greatly facilitate the study of genetic modifications in the mouse brain.