Neuroprotective effect of the immune system in a mouse model of severe dysmyelinating hereditary neuropathy: enhanced axonal degeneration following disruption of the RAG-1 gene

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Abstract From Mol Cell Neurosci. 2005 Jan;28(1):118-27.

Neuroprotective effect of the immune system in a mouse model of severe

dysmyelinating hereditary neuropathy: enhanced axonal degeneration following

disruption of the RAG-1 gene.

Berghoff M, Samsam M, Muller M, Kobsar I, Toyka KV, Kiefer R, Maurer M, i

R.

Section of Developmental Neurobiology, Department of Neurology, University of

Wurzburg, 97080 Wurzburg, Germany.

In mouse models of later onset forms of human hereditary demyelinating

neuropathies, the immune system plays a crucial pathogenic role. Here, we

investigated the influence of immune cells on early onset dysmyelination in mice

homozygously deficient of the myelin component P0. In peripheral nerves of

P0(-/-) mice, CD8+ T-lymphocytes increased with age. Macrophages peaked at 3

months followed by a substantial decline. They were mainly of hematogenous

origin. To evaluate the functional role of immune cells, we cross-bred P0(-/-)

mutants with RAG-1-deficient mice. At 3 months, the number of endoneurial

macrophages did not differ from the macrophage number of immunocompetent myelin

mutants, but the later decline of macrophages was not observed. Quantitative

electron microscopy revealed that in plantar nerves of 6-month-old double

mutants, significantly more axons had degenerated than in immunocompetent

littermates. These data suggest a neuroprotective net effect of T-lymphocytes on

axon survival in inherited, early onset dysmyelination.