Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice.
A central hypothesis for the limited capacity for adult central nervous system (CNS) axons to regenerate is the presence of myelin-derived axon growth inhibitors, the role of which, however, remains poorly understood. We have conducted a comprehensive genetic analysis of the three major myelin inhibitors, Nogo, MAG, and OMgp, in injury-induced axonal growth, including compensatory sprouting of uninjured axons and regeneration of injured axons. While deleting any one inhibitor in mice enhanced sprouting of corticospinal or raphespinal serotonergic axons, there was neither associated behavioral improvement nor a synergistic effect of deleting all three inhibitors. Furthermore, triple-mutant mice failed to exhibit enhanced regeneration of either axonal tract after spinal cord injury. Our data indicate that while Nogo, MAG, and OMgp may modulate axon sprouting, they do not play a central role in CNS axon regeneration failure.
Lee
Jae K
JK
Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Geoffroy
Cédric G
CG
Chan
Andrea F
AF
Tolentino
Kristine E
KE
Crawford
Michael J
MJ
Leal
Marisa A
MA
Kang
Brian
B
Zheng
Binhai
B
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D002478:Cells, Cultured; D058851:GPI-Linked Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009185:Myelin Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D018992:Myelin-Associated Glycoprotein / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D000070798:Nogo Proteins; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D013116:Spinal Cord / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
D058851:GPI-Linked Proteins; C104739:Mag protein, mouse; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D000070798:Nogo Proteins; C560529:Omg protein, mouse; D011956:Receptors, Cell Surface; C000603201:Rtn4 protein, mouse