Nature Reviews Neuroscience, Aug 2006

Nerve Regeneration – A strain on regeneration


Rowan A

One of the key factors that blocks axonal regrowth following injury to the mature CNS is Nogo-A, a protein that is highly expressed in adult CNS myelin and inhibits neurite growth. In new work reported in The Journal of Neuroscience, Martin Schwab and colleagues showed surprising variability between two strains of Nogo-A-deficient mice in the extent of regeneration following corticospinal tract injury, which was attributable to differences in the expression of genes related to neurite outgrowth and synapse formation.

Preventing the action of Nogo-A by using neutralizing antibodies or by blocking the Nogo-A receptor subunit NgR in mature rodents permits considerable regrowth of damaged spinal cord fibre tracts and leads to restoration of function. However, there have been mixed findings from studies of Nogo-A-knockout mice, with some, but not all, reporting regeneration, despite using the same cell types and strains of mice — that is, chimeric mice generated from 129X1/SvJ embryonic stem cells that were implanted into C57BL/6 blastocytes.

In these studies, the fraction of 129X1/SvJ and C57BL/6 genetic background in the different mouse lines was not determined, and it could be that genetic differences explain the conflicting findings between studies. Schwab and his team investigated this possibility by creating Nogo-A-specific knockouts in pure.

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