Mature oligodendrocytes are critical for myelin maintenance. To understand the molecular basis for this, genetic manipulation of mature oligodendrocytes is needed. Here we generated a mature oligodendrocyte tTA (tetracycline-controlled transcriptional activator) mouse line which, in combination with a tTA-dependent promoter line driving the expression of the desired transgene, can be used for gain-of-function studies. We used an oligodendrocyte promoter, the mouse proteolipid protein (PLP) promoter, to express mammalianized tTA, and generated a PLP-mtTA mouse line. In adults, mtTA mRNA was predominantly detected in brain white matter where it co-localized with PLP mRNA. mtTA-mediated gene induction was confirmed by crossing to mice with a tTA-dependent promoter driving expression of yellow fluorescent protein (tetO-YFP mice). YFP induction in PLP-mtTA::tetO-YFP mice was consistent with PLP expression in adult mature oligodendrocytes and premyelinating-stage myelinating oligodendrocytes. This PLP-mtTA mouse line is the first to enable gain-of-function studies in mature oligodendrocytes with the tet system.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/dvg.20808 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Therapeutic reduction of neurocan in murine intracerebral hemorrhage lesions promotes oligodendrogenesis and functional recovery.
J Neuroinflammation
January 2025
Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, 2 Jingba Road, Zhengzhou, Henan, China.
Background: Intracerebral hemorrhage (ICH) causes prominent deposition of extracellular matrix molecules, particularly the chondroitin sulphate proteoglycan (CSPG) member neurocan. In tissue culture, neurocan impedes the properties of oligodendrocytes. Whether therapeutic reduction of neurocan promotes oligodendrogenesis and functional recovery in ICH is unknown.
View Article and Find Full Text PDFThe Role of Oligodendrocyte Lineage Cells in the Pathogenesis of Alzheimer's Disease.
Neurochem Res
January 2025
Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Alzheimer's disease (AD) is a central nervous system degenerative disease with a stealthy onset and a progressive course characterized by memory loss, cognitive dysfunction, and abnormal psychological and behavioral symptoms. However, the pathogenesis of AD remains elusive. An increasing number of studies have shown that oligodendrocyte progenitor cells (OPCs) and oligodendroglial lineage cells (OLGs), especially OPCs and mature oligodendrocytes (OLGs), which are derived from OPCs, play important roles in the pathogenesis of AD.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
John P. Hussman Institute for Human Genomics, Miami, FL, USA.
Background: Genome-wide association studies (GWAS) in Alzheimer's disease (AD) are consistently discovering genetic variants linked to the risk of developing this neurodegenerative condition. However, the effect size of the shared associated loci varies across populations as well as each population can have unique associations. This phenomenon could be explained by ancestry-dependent changes in the genomic regulatory architecture (GRA) influencing the expression of these genes, similar to the effect of different local ancestry on the risk of AD in APOE4 carriers.
View Article and Find Full Text PDFEffect of Cytoskeletal Linker Protein GAS2L1 on Oligodendrocyte and Myelin Development.
Glia
January 2025
Key Laboratory of Brain, Cognition and Education Sciences of Ministry of Education; Institute for Brain Research and Rehabilitation, Guangdong Key Laboratory of Mental Health and Cognitive Science, and Center for Studies of Psychological Application, South China Normal University, Guangzhou, China.
Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system (CNS), develop from OL precursor cells (OPCs) through a complex process involving significant morphological changes that are critically dependent on the dynamic interactions between cytoskeletal networks. Growth arrest-specific 2-like protein 1 (GAS2L1) is a cytoskeletal linker protein that mediates the cross-talk between actin filaments and microtubules. However, its role in OL and myelin development remains unknown.
View Article and Find Full Text PDFBrain-wide cell-type-specific transcriptomic signatures of healthy ageing in mice.
Nature
January 2025
Allen Institute for Brain Science, Seattle, WA, USA.
Article Synopsis
- Biological aging involves a gradual loss of homeostasis in molecular and cellular functions, particularly in the brain, which contains diverse cell types that differ in their aging resilience.
- This study offers an extensive single-cell RNA sequencing dataset of approximately 1.2 million transcriptomes from brain cells in young and aged mice, identifying 847 cell clusters and 14 age-biased clusters predominantly involving glial types.
- Key findings reveal specific gene expression changes with aging, including decreased neuronal function genes and increased immune-related genes, particularly in cells around the third ventricle of the hypothalamus, suggesting its critical role in the aging process of the mouse brain.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!