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The Journal of Neuroscience, May 24, 2006, 26(21):5591-5603; doi:10.1523/JNEUROSCI.1103-06.2006
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Neurobiology of Disease
Nogo-A-Deficient Mice Reveal Strain-Dependent Differences in Axonal Regeneration
Leda Dimou, * Lisa Schnell, * Laura Montani, Carri Duncan, Marjo Simonen, Regula Schneider, Thomas Liebscher, Miriam Gullo, andMartin E. Schwab Brain Research Institute, University of Zurich and Department Biology, Swiss Federal Institute of Technology, CH-8057 Zurich, Switzerland
Correspondence should be addressed to Leda Dimou at her present address: Physiological Genomics, Ludwig-Maximilians-Universität Munich, Pettenkoferstrasse 12, 80336 Munich, Germany. Email: leda.dimou{at}lrz.uni-muenchen.de
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.
Key words: CNS repair; Nogo; mouse strain; regeneration; spinal cord injury; neurite outgrowth
Received Oct. 17, 2005; accepted April 11, 2006.
Correspondence should be addressed to Leda Dimou at her present address: Physiological Genomics, Ludwig-Maximilians-Universität Munich, Pettenkoferstrasse 12, 80336 Munich, Germany. Email: leda.dimou{at}lrz.uni-muenchen.de
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