Transgenic inhibition of Nogo-66 receptor function allows axonal sprouting and improved locomotion after spinal injury.

Axon growth after spinal injury is thought to be limited in part by myelin-derived proteins that act via the Nogo-66 Receptor (NgR). To test this hypothesis, we sought to study recovery from spinal cord injury (SCI) after inhibiting NgR transgenically with a soluble function-blocking NgR fragment. Glial fibrillary acidic protein (gfap) gene regulatory elements were used to generate mice that secrete NgR(310)ecto from astrocytes. After mid-thoracic dorsal over-hemisection injury, gfap::ngr(310)ecto mice exhibit enhanced raphespinal and corticospinal axonal sprouting into the lumbar spinal cord. Recovery of locomotion is improved in the gfap::ngr(310)ecto mice. These data indicate that the NgR ligands, Nogo-66, MAG, and OMgp, play a role in limiting axonal growth in the injured adult CNS and that NgR(310)ecto might provide a therapeutic means to promote recovery from SCI.