title: 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.
abstract: 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.
authors.affiliation: Section of Developmental Neurobiology, Department of Neurology, University of Würzburg, 97080 Würzburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Berghoff
authors.forename: Mohtashem
authors.initials: M
authors.lastname: Samsam
authors.forename: Marcus
authors.initials: M
authors.lastname: Müller
authors.forename: Igor
authors.initials: I
authors.lastname: Kobsar
authors.forename: Klaus V
authors.initials: KV
authors.lastname: Toyka
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kiefer
authors.forename: Mathias
authors.initials: M
authors.lastname: Mäurer
authors.forename: Rudolf
authors.initials: R
authors.lastname: Martini
mesh_terms: D000367:Age Factors; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000235:genetics / Q000276:immunology; D003711:Demyelinating Diseases / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D004195:Disease Models, Animal; D016654:Genes, RAG-1 / Q000235:genetics*; D007107:Immune System / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D018993:Myelin P0 Protein / Q000172:deficiency / Q000235:genetics; D010525:Peripheral Nerves / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D013979:Tibial Nerve / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D014855:Wallerian Degeneration / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology
chemical_list: D018993:Myelin P0 Protein