{"doi":"10.1523/jneurosci.1069-12.2012","title":"Myelin Gene Regulatory Factor Is Required for Maintenance of Myelin and Mature Oligodendrocyte Identity in the Adult CNS","abstract":"<jats:p>Although the transcription factors required for the generation of oligodendrocytes and CNS myelination during development have been relatively well established, it is not known whether continued expression of the same factors is required for the maintenance of myelin in the adult. Here, we use an inducible conditional knock-out strategy to investigate whether continued oligodendrocyte expression of the recently identified transcription factor myelin gene regulatory factor (MRF) is required to maintain the integrity of myelin in the adult CNS. Genetic ablation of MRF in mature oligodendrocytes within the adult CNS resulted in a delayed but severe CNS demyelination, with clinical symptoms beginning at 5 weeks and peaking at 8 weeks after ablation of MRF. This demyelination was accompanied by microglial/macrophage infiltration and axonal damage. Transcripts for myelin genes, such as proteolipid protein, MAG, MBP, and myelin oligodendrocyte glycoprotein, were rapidly downregulated after ablation of MRF, indicating an ongoing requirement for MRF in the expression of these genes. Subsequently, a proportion of the recombined oligodendrocytes undergo apoptosis over a period of weeks. Surviving oligodendrocytes gradually lose the expression of mature markers such as CC1 antigen and their association with myelin, without reexpressing oligodendrocyte progenitor markers or reentering the cell cycle. These results demonstrate that ongoing expression of MRF within the adult CNS is critical to maintain mature oligodendrocyte identity and the integrity of CNS myelin.</jats:p>","journal":"The Journal of Neuroscience","year":2012,"id":33237,"datarank":8.421338372782788,"base_score":5.41610040220442,"endowment":5.41610040220442,"self_citation_contribution":0.8124150603306631,"citation_network_contribution":7.6089233124521245,"self_endowment_contribution":0.8124150603306631,"citer_contribution":7.6089233124521245,"corpus_percentile":null,"corpus_rank":null,"citation_count":224,"citer_count":200,"citers_with_citation_signal":173,"citers_with_endowment":173,"datacite_reuse_total":18,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":174383,"name":"Stacey Jackson","orcid":null,"position":1,"is_corresponding":false},{"id":174385,"name":"Curtis M. Hay","orcid":null,"position":2,"is_corresponding":false},{"id":174387,"name":"Clare Faux","orcid":null,"position":3,"is_corresponding":false},{"id":95080,"name":"Trevor J. Kilpatrick","orcid":"0000-0003-3999-085X","position":4,"is_corresponding":false},{"id":174389,"name":"Melanie Willingham","orcid":null,"position":5,"is_corresponding":false},{"id":174391,"name":"Ben Emery","orcid":null,"position":6,"is_corresponding":false},{"id":174382,"name":"Matthias Koenning","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.41610040220442,"endowment":5.41610040220442,"datacite_reuse_total":18,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22956843","pmcid":"PMC3752083","openalex_id":"https://openalex.org/W2072990016","authors":[],"funders":[{"funder_name":"NEI NIH HHS","grant_id":"R01 EY010257","title":null},{"funder_name":"NEI NIH HHS","grant_id":"R29 EY010257","title":null},{"funder_name":"NEI NIH HHS","grant_id":"EY10257","title":null}],"total_grants":3,"fwci":5.169,"citation_percentile":0.95944755,"influential_citations":12,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":10},{"year":2014,"count":9},{"year":2015,"count":13},{"year":2016,"count":17},{"year":2017,"count":19},{"year":2018,"count":12},{"year":2019,"count":19},{"year":2020,"count":18},{"year":2021,"count":16},{"year":2022,"count":16},{"year":2023,"count":32},{"year":2024,"count":20},{"year":2025,"count":18},{"year":2026,"count":3}],"oa_status":"bronze","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","oa_locations":[{"url":"https://www.jneurosci.org/content/jneuro/32/36/12528.full.pdf","host_type":"journal"},{"url":"https://www.jneurosci.org/content/jneuro/32/36/12528.full.pdf","host_type":"HYBRID"},{"url":"https://www.jneurosci.org/content/jneuro/32/36/12528.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1523/JNEUROSCI.1069-12.2012","host_type":"publisher"},{"url":"https://doi.org/10.1523/jneurosci.1069-12.2012","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22956843","host_type":"repository"},{"url":"http://europepmc.org/articles/PMC3752083","host_type":"repository"},{"url":"http://hdl.handle.net/11343/41290","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3752083","host_type":"repository"}],"fields_of_study":["Neurogenesis and neuroplasticity mechanisms","Neurogenetic and Muscular Disorders Research","RNA Research and Splicing","Biology","Medicine","Age Factors","Animals","Cell Differentiation","Central Nervous System","Demyelinating Diseases","Mice","Mice, 129 Strain","Mice, Inbred C57BL","Mice, Knockout","Myelin Sheath","Oligodendroglia","Transcription Factors"],"mesh_terms":["Age Factors","Animals","Cell Differentiation","Central Nervous System","Demyelinating Diseases","Mice, Inbred C57BL","Myelin Sheath","Oligodendroglia","Transcription Factors","Mice, Knockout","Mice","Mice, 129 Strain"],"keywords":["Myelin","Oligodendrocyte","Biology","Myelin oligodendrocyte glycoprotein","Cell biology","Myelin-associated glycoprotein","Myelin basic protein","OLIG2","Transcription factor","Proteolipid protein 1","Neuroscience","Immunology","Central nervous system","Gene","Genetics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.22606046.v1","title":"Additional file 1 of ANGPTL2 binds MAG to efficiently enhance oligodendrocyte differentiation","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.22606046","title":"Additional file 1 of ANGPTL2 binds MAG to efficiently enhance oligodendrocyte differentiation","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.22606049.v1","title":"Additional file 2 of ANGPTL2 binds MAG to efficiently enhance oligodendrocyte differentiation","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.22606052.v1","title":"Additional file 3 of ANGPTL2 binds MAG to efficiently enhance oligodendrocyte differentiation","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.22606049","title":"Additional file 2 of ANGPTL2 binds MAG to efficiently enhance oligodendrocyte differentiation","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.22606052","title":"Additional file 3 of ANGPTL2 binds MAG to efficiently enhance oligodendrocyte differentiation","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.22631433.v1","title":"Additional file 1 of Stalled oligodendrocyte differentiation in IDH-mutant gliomas","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.22631433","title":"Additional file 1 of Stalled oligodendrocyte differentiation in IDH-mutant gliomas","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.25038074.v1","title":"Additional file 1 of Microglia-derived exosomes modulate myelin regeneration via miR-615-5p/MYRF axis","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.25038074","title":"Additional file 1 of Microglia-derived exosomes modulate myelin regeneration via miR-615-5p/MYRF axis","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.22631436.v1","title":"Additional file 2 of Stalled oligodendrocyte differentiation in IDH-mutant gliomas","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.22631445.v1","title":"Additional file 5 of Stalled oligodendrocyte differentiation in IDH-mutant gliomas","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.22631436","title":"Additional file 2 of Stalled oligodendrocyte differentiation in IDH-mutant gliomas","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.22631439.v1","title":"Additional file 3 of Stalled oligodendrocyte differentiation in IDH-mutant gliomas","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.22631442.v1","title":"Additional file 4 of Stalled oligodendrocyte differentiation in IDH-mutant gliomas","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.22631445","title":"Additional file 5 of Stalled oligodendrocyte differentiation in IDH-mutant gliomas","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.22631442","title":"Additional file 4 of Stalled oligodendrocyte differentiation in IDH-mutant gliomas","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.22631439","title":"Additional file 3 of Stalled oligodendrocyte differentiation in IDH-mutant gliomas","publisher":"figshare","resource_type":"Dataset"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-09T15:54:56.944002Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}