title: Transgenic inhibition of Nogo-66 receptor function allows axonal sprouting and improved locomotion after spinal injury.
abstract: 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.
authors.affiliation: Department of Neurology, Yale University School of Medicine, PO Box 208018, New Haven, CT 06510, USA.
authors.forename: Shuxin
authors.initials: S
authors.lastname: Li
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Stephane
authors.initials: S
authors.lastname: Budel
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Hampton
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Strittmatter
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D005260:Female; D058851:GPI-Linked Proteins; D015316:Genetic Therapy / Q000379:methods*; D008124:Locomotion; D051379:Mice; D008822:Mice, Transgenic; D009185:Myelin Proteins / Q000235:genetics* / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000502:physiology*; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000628:therapy*
chemical_list: D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C419790:Rtn4r protein, mouse