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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, and Martin 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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