Myelin basic protein mRNA levels affect myelin sheath dimensions, architecture, plasticity, and density of resident glial cells.
Myelin Basic Protein (MBP) is essential for both elaboration and maintenance of CNS myelin, and its reduced accumulation results in hypomyelination. How different Mbp mRNA levels affect myelin dimensions across the lifespan and how resident glial cells may respond to such changes are unknown. Here, to investigate these questions, we used enhancer-edited mouse lines that accumulate Mbp mRNA levels ranging from 8% to 160% of wild type. In young mice, reduced Mbp mRNA levels resulted in corresponding decreases in Mbp protein accumulation and myelin sheath thickness, confirming the previously demonstrated rate-limiting role of Mbp transcription in the control of initial myelin synthesis. However, despite maintaining lower line specific Mbp mRNA levels into old age, both MBP protein levels and myelin thickness improved or fully normalized at rates defined by the relative Mbp mRNA level. Sheath length, in contrast, was affected only when mRNA levels were very low, demonstrating that sheath thickness and length are not equally coupled to Mbp mRNA level. Striking abnormalities in sheath structure also emerged with reduced mRNA levels. Unexpectedly, an increase in the density of all glial cell types arose in response to reduced Mbp mRNA levels. This investigation extends understanding of the role MBP plays in myelin sheath elaboration, architecture, and plasticity across the mouse lifespan and illuminates a novel axis of glial cell crosstalk.
Pubmed ID: 39023138 RIS Download
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- GST-pi (RRID:AB_591792)
- Mouse PDGF R alpha Antibody (RRID:AB_2236897)
- DyLight 405-AffiniPure Donkey Anti-Chicken IgY (IgG) (H+L) (min X Bov,Gt,GP,Sy Hms,Hrs,Hu,Ms,Rb,Rat,Shp Sr Prot) (RRID:AB_2340373)
- Donkey Anti-Rabbit IgG (H+L) Antibody, Alexa Fluor ?? 488 Conjugated (RRID:AB_2535792)
- Caspr antibody (RRID:AB_869934)
- Donkey Anti-Mouse IgG (H+L) Polyclonal Antibody, Alexa Fluor ?? 647 Conjugated (RRID:AB_162542)
- MAG (C-19) (RRID:AB_670102)
- Purified anti-Neurofilament H (NF-H) (RRID:AB_2564859)
- Cy3-AffiniPure Bovine Anti-Goat IgG (H+L) (min X Bov,Ck,GP,Sy Hms,Hrs,Hu,Ms,Rb,Rat Sr Prot) (RRID:AB_2340880)
- Anti-APC (Ab-7) Mouse mAb (CC-1) (RRID:AB_2057371)
Associated grants
- Agency: Healthy Brains for Healthy Lives Innovative Ideas Project Grant,
- Agency: Fonds de Recherche du Québec - Santé,
Id: 312947 - Agency: Canada First Research Excellence Fund (CFREF),
- Agency: NIH HHS, United States
Id: S10 OD016435 - Agency: Natural Sciences and Engineering Research Council of Canada (NSERC),
Id: RGPIN-2018-05047 - Agency: NIH HHS, United States
Id: R01NS116182 - Agency: Natural Sciences and Engineering Research Council of Canada (NSERC),
Id: RGPIN-2019-06973
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Microsoft Excel (tool)
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Software application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.
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Microsoft system includes integrated digital inverted benchtop microscope for four-color fluorescence, transmitted-light, and color imaging. Provides interchangeable optics with autofocus, single-click multi-channel image acquisition.3.2 Megapixels, monochrome, CMOS camera. Offers software for acquisition, analysis, and automated cell counting.
View all literature mentionsMouse PDGF R alpha Antibody (antibody)
RRID:AB_2236897
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RRID:AB_2340373
This unknown targets Chicken IgY (IgG) (H+L)
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This polyclonal targets Rat Caspr
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This polyclonal targets Mouse IgG (H+L)
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This unknown targets Neurofilament H NF-H
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RRID:AB_2340880
This unknown targets Goat IgG (H+L)
View all literature mentionsAnti-APC (Ab-7) Mouse mAb (CC-1) (antibody)
RRID:AB_2057371
This monoclonal targets APC
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