Targeted disruption of the galanin gene reduces the number of sensory neurons and their regenerative capacity

The neuropeptide galanin is expressed developmentally in the dorsal root ga nglion (DRG) and is rapidly up-regulated 120-fold after peripheral nerve se ction in the adult. Here we report that adult mice carrying a loss-of-funct ion mutation in the galanin gene have a 13% reduction in the number of cell s in the DRG associated with a 24% decrease in the percentage of neurons th at express substance P. These deficits are associated with a 2.8- and 2.6-f old increase in the number of apoptotic cells in the DRG at postnatal days 3 and 4. respectively. After crush injury to the sciatic nerve, the rate of peripheral nerve regeneration is reduced by 35% with associated long-term functional deficits. Cultured DRG neurons from adult mutant mice demonstrat e similar deficits in neurite number and length. These results identify a c ritical role for galanin in the development and regeneration of sensory neu rons.