Deletion of Jun proteins in adult oligodendrocytes does not perturb cell survival, or myelin maintenance in vivo

Bettina Schreiner; Barbara Ingold-Heppner; Debora Pehl; Giuseppe Locatelli; Helia Berrit-Schönthaler; Burkhard Becher

doi:10.1371/journal.pone.0120454

Deletion of Jun proteins in adult oligodendrocytes does not perturb cell survival, or myelin maintenance in vivo

PLoS One. 2015 Mar 16;10(3):e0120454. doi: 10.1371/journal.pone.0120454. eCollection 2015.

Authors

Bettina Schreiner¹, Barbara Ingold-Heppner², Debora Pehl³, Giuseppe Locatelli⁴, Helia Berrit-Schönthaler⁵, Burkhard Becher⁶

Affiliations

¹ Institute of Experimental Immunology, University Zürich, Zürich, Switzerland; Department of Neurology, University Hospital Zürich, Zürich, Switzerland.
² Institute of Pathology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
³ Institute of Neuropathology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
⁴ Institute of Experimental Immunology, University Zürich, Zürich, Switzerland; Institute of Clinical Neuroimmunology, LMU Universität München, Germany.
⁵ Spanish National Cancer Research Center, Madrid, Spain.
⁶ Institute of Experimental Immunology, University Zürich, Zürich, Switzerland.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / metabolism
Cell Survival / genetics*
Cuprizone / adverse effects
Demyelinating Diseases / chemically induced
Demyelinating Diseases / genetics
Demyelinating Diseases / metabolism
Encephalomyelitis, Autoimmune, Experimental / genetics
Encephalomyelitis, Autoimmune, Experimental / metabolism
Encephalomyelitis, Autoimmune, Experimental / pathology
Female
Mice
Mice, Knockout
Motor Activity / genetics
Oligodendroglia / metabolism*
Phenotype
Proto-Oncogene Proteins c-jun / deficiency*
Proto-Oncogene Proteins c-jun / genetics
Proto-Oncogene Proteins c-jun / metabolism
Transcription Factors / deficiency*
Transcription Factors / genetics
Transcription Factors / metabolism

Substances

JunB protein, mouse
Proto-Oncogene Proteins c-jun
Transcription Factors
Cuprizone

Grants and funding

This study was supported by grants from the Swiss National Science Foundation (316030_150768 (BB), 310030_146130 (BB), CRSII3_136203 (BB) and SPUM 33CM30-124111/1 (BB, BS)), European Union FP7 project TargetBraIn, NeuroKine and ATECT (BB), the university research priority project translational cancer research (BB) and “Stiftung für Forschung an der Medizinischen Fakultät” (BS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.