title: Immune deficiency in mouse models for inherited peripheral neuropathies leads to improved myelin maintenance.
abstract: The adhesive cell surface molecule P(0) is the most abundant glycoprotein in peripheral nerve myelin and fulfills pivotal functions during myelin formation and maintenance. Mutations in the corresponding gene cause hereditary demyelinating neuropathies. In mice heterozygously deficient in P(0) (P(0)(+/-) mice), an established animal model for a subtype of hereditary neuropathies, T-lymphocytes are present in the demyelinating nerves. To monitor the possible involvement of the immune system in myelin pathology, we cross-bred P(0)(+/-) mice with null mutants for the recombination activating gene 1 (RAG-1) or with mice deficient in the T-cell receptor alpha-subunit. We found that in P(0)(+/-) mice myelin degeneration and impairment of nerve conduction properties is less severe when the immune system is deficient. Moreover, isolated T-lymphocytes from P(0)(+/-) mice show enhanced reactivity to myelin components of the peripheral nerve, such as P(0), P(2), and myelin basic protein. We hypothesize that autoreactive immune cells can significantly foster the demyelinating phenotype of mice with a primarily genetically based peripheral neuropathy.
authors.affiliation: Department of Neurology, University of Würzburg, D-97080 Würzburg, Germany.
authors.forename: C D
authors.initials: CD
authors.lastname: Schmid
authors.forename: M
authors.initials: M
authors.lastname: Stienekemeier
authors.forename: S
authors.initials: S
authors.lastname: Oehen
authors.forename: F
authors.initials: F
authors.lastname: Bootz
authors.forename: J
authors.initials: J
authors.lastname: Zielasek
authors.forename: R
authors.initials: R
authors.lastname: Gold
authors.forename: K V
authors.initials: KV
authors.lastname: Toyka
authors.forename: M
authors.initials: M
authors.lastname: Schachner
authors.forename: R
authors.initials: R
authors.lastname: Martini
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D003711:Demyelinating Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D016654:Genes, RAG-1; D019673:Genes, T-Cell Receptor alpha; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D018993:Myelin P0 Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009186:Myelin Sheath / Q000473:pathology / Q000502:physiology; D009410:Nerve Degeneration; D009431:Neural Conduction; D010525:Peripheral Nerves / Q000276:immunology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018398:Homeodomain Proteins; D018993:Myelin P0 Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064658:RAG-1 protein