Nogo-A-deficient mice reveal strain-dependent differences in axonal regeneration.
Nogo-A, a membrane protein enriched in myelin of the adult CNS, inhibits neurite growth and regeneration; neutralizing antibodies or receptor blockers enhance regeneration and plasticity in the injured adult CNS and lead to improved functional outcome. Here we show that Nogo-A-specific knock-outs in backcrossed 129X1/SvJ and C57BL/6 mice display enhanced regeneration of the corticospinal tract after injury. Surprisingly, 129X1/SvJ Nogo-A knock-out mice had two to four times more regenerating fibers than C57BL/6 Nogo-A knock-out mice. Wild-type newborn 129X1/SvJ dorsal root ganglia in vitro grew a much higher number of processes in 3 d than C57BL/6 ganglia, confirming the stronger endogenous neurite growth potential of the 129X1/SvJ strain. cDNA microarrays of the intact and lesioned spinal cord of wild-type as well as Nogo-A knock-out animals showed a number of genes to be differentially expressed in the two mouse strains; many of them belong to functional categories associated with neurite growth, synapse formation, and inflammation/immune responses. These results show that neurite regeneration in vivo, under the permissive condition of Nogo-A deletion, and neurite outgrowth in vitro differ significantly in two widely used mouse strains and that Nogo-A is an important endogenous inhibitor of axonal regeneration in the adult spinal cord.
Dimou
Leda
L
Brain Research Institute, University of Zurich, Department Biology, Swiss Federal Institute of Technology, CH-8057 Zurich, Switzerland. leda.dimou@lrz.uni-muenchen.de
Schnell
Lisa
L
Montani
Laura
L
Duncan
Carri
C
Simonen
Marjo
M
Schneider
Regula
R
Liebscher
Thomas
T
Gullo
Miriam
M
Schwab
Martin E
ME
D000818:Animals; D001369:Axons / Q000000981:diagnostic imaging / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009185:Myelin Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D016501:Neurites / Q000502:physiology* / Q000648:ultrastructure; D000070798:Nogo Proteins; D013045:Species Specificity; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D014463:Ultrasonography
D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603201:Rtn4 protein, mouse