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The role of macrophages in demyelinating peripheral nervous system of mice heterozygously deficient in P0

Carenini, S; Maurer, M; Werner, A; Blazyca, H; Toyka, KV; Schmid, CD; Raivich, G; (2001) The role of macrophages in demyelinating peripheral nervous system of mice heterozygously deficient in P0. J CELL BIOL , 152 (2) 301 - 308.

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Abstract

Mice heterozygously deficient in the p0 gene (P0(+/-)) are animal models for some forms of inherited neuropathies. They display a progressive demyelinating phenotype in motor nerves, accompanied by mild infiltration of lymphocytes and increase in macrophages, We have shown previously that the T lymphocytes are instrumental in the demyelination process. This study addresses the functional role of the macrophage in this monogenic myelin disorder.In motor nerves of P0(+/-) mice, the number of macrophages in demyelinated peripheral nerves was increased by a factor of five when compared with motor nerves of wild-type mice. Immunoelectron microscopy, using a specific marker for mouse macrophages, displayed macrophages not only in the endoneurium of the myelin mutants, but also within endoneurial tubes, suggesting an active role in demyelination. To elucidate the roles of the macrophages, we crossbred the myelin mutants with a spontaneous mouse mutant deficient in macrophage colony-stimulating factor (M-CSF), hence displaying impaired macrophage activation. In the P0-deficient double mutants also deficient in M-CSF, the numbers of macrophages Mere not elevated in the demyelinating motor nerves and demyelination was less severe. These findings demonstrate an active role of macrophages during pathogenesis of inherited demyelination with putative impact on future treatment strategies.

Type: Article
Title: The role of macrophages in demyelinating peripheral nervous system of mice heterozygously deficient in P0
Keywords: macrophage, macrophage colony-stimulating factor, myelin degeneration, Schwann cell, inherited neuropathies, MARIE-TOOTH-DISEASE, GUILLAIN-BARRE-SYNDROME, HEREDITARY MOTOR, SENSORY NEUROPATHY, 17P DUPLICATION, SCHWANN-CELLS, MYELIN GENES, MOUSE, EXPRESSION, MICROGLIA
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst for Women's Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Inst for Women's Health > Maternal and Fetal Medicine
URI: http://discovery.ucl.ac.uk/id/eprint/26167
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