title: Attenuated demyelination in the absence of the macrophage-restricted adhesion molecule sialoadhesin (Siglec-1) in mice heterozygously deficient in P0.
abstract: Mouse mutants heterozygously deficient for the myelin component P0 mimic some forms of inherited neuropathies in humans. We have previously shown that both T lymphocytes and macrophages contribute to the demyelinating neuropathy. Both cell types appear to influence each other mutually, i.e., impaired T lymphocyte development in RAG-1-deficient P0 mutants leads to decreased macrophage numbers and retarded macrophage activation causes reduced T lymphocyte numbers in the peripheral nerves of P0(+/-) mice. In the present study, we investigated the possible role of the macrophage-restricted sialic acid-binding Ig-like lectin sialoadhesin (Sn, Siglec-1) in the pathogenesis of inherited demyelination in P0(+/-) mice. We found that most peripheral nerve macrophages express Sn in the mutants. Myelin mutants devoid of Sn show reduced numbers of CD8+ T lymphocytes and macrophages in peripheral nerves and less severe demyelination, resulting in improved nerve conduction properties. Our findings are potentially important in the development of future treatment strategies for inherited demyelinating neuropathies.
authors.affiliation: Department of Neurology, Developmental Neurobiology, University of Wuerzburg, Josef-Schneider-Str. 11, D-97080 Wuerzburg, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Kobsar
authors.forename: Cornelia
authors.initials: C
authors.lastname: Oetke
authors.forename: Antje
authors.initials: A
authors.lastname: Kroner
authors.forename: Carsten
authors.initials: C
authors.lastname: Wessig
authors.forename: Paul
authors.initials: P
authors.lastname: Crocker
authors.forename: Rudolf
authors.initials: R
authors.lastname: Martini
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002607:Charcot-Marie-Tooth Disease / Q000473:pathology / Q000503:physiopathology; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004594:Electrophysiology; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018993:Myelin P0 Protein / Q000235:genetics / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology*; D010525:Peripheral Nerves / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D010641:Phenotype; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D063267:Sialic Acid Binding Ig-like Lectin 1
chemical_list: D008562:Membrane Glycoproteins; D018993:Myelin P0 Protein; D011971:Receptors, Immunologic; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1; C571167:Siglec1 protein, mouse