title: Deletion of Jun proteins in adult oligodendrocytes does not perturb cell survival, or myelin maintenance in vivo.
abstract: Oligodendrocytes, the myelin-forming glial cells of the central nervous system (CNS), are fundamental players in rapid impulse conduction and normal axonal functions. JunB and c-Jun are DNA-binding components of the AP-1 transcription factor, which is known to regulate different processes such as proliferation, differentiation, stress responses and death in several cell types, including cultured oligodendrocyte/lineage cells. By selectively inactivating Jun B and c-Jun in myelinating oligodendrocytes in vivo, we generated mutant mice that developed normally, and within more than 12 months showed normal ageing and survival rates. In the adult CNS, absence of JunB and c-Jun from mature oligodendrocytes caused low-grade glial activation without overt signs of demyelination or secondary leukocyte infiltration into the brain. Even after exposure to toxic or autoimmune oligodendrocyte insults, signs of altered oligodendrocyte viability were mild and detectable only upon cuprizone treatment. We conclude that JunB and c-Jun expression in post-mitotic oligodendrocytes is mostly dispensable for the maintainance of white matter tracts throughout adult life, even under demyelinating conditions.
authors.affiliation: Institute of Experimental Immunology, University Zürich, Zürich, Switzerland; Department of Neurology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Bettina
authors.initials: B
authors.lastname: Schreiner
authors.affiliation: Institute of Pathology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ingold-Heppner
authors.affiliation: Institute of Neuropathology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Debora
authors.initials: D
authors.lastname: Pehl
authors.affiliation: Institute of Experimental Immunology, University Zürich, Zürich, Switzerland; Institute of Clinical Neuroimmunology, LMU Universität München, Germany.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Locatelli
authors.affiliation: Spanish National Cancer Research Center, Madrid, Spain.
authors.forename: Helia
authors.initials: H
authors.lastname: Berrit-Schönthaler
authors.affiliation: Institute of Experimental Immunology, University Zürich, Zürich, Switzerland.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Becher
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics*; D003471:Cuprizone / Q000009:adverse effects; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009836:Oligodendroglia / Q000378:metabolism*; D010641:Phenotype; D016755:Proto-Oncogene Proteins c-jun / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: C584097:JunB protein, mouse; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D003471:Cuprizone