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

Mol Cell Neurosci. 2005 May;29(1):26-39. doi: 10.1016/j.mcn.2004.12.008.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axons / physiology*
  • Female
  • GPI-Linked Proteins
  • Genetic Therapy / methods*
  • Locomotion
  • Mice
  • Mice, Transgenic
  • Myelin Proteins / genetics*
  • Myelin Proteins / physiology*
  • Nerve Regeneration / physiology*
  • Nogo Receptor 1
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / physiology*
  • Recovery of Function
  • Spinal Cord Injuries / physiopathology*
  • Spinal Cord Injuries / therapy*


  • GPI-Linked Proteins
  • Myelin Proteins
  • Nogo Receptor 1
  • Receptors, Cell Surface
  • Rtn4r protein, mouse