ArticleGlia2020
The failure of microglia to digest developmental apoptotic cells contributes to the pathology of RNASET2-deficient leukoencephalopathy.
Article in Glia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
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- Zebrafish in neurodevelopmental disorders studies: Genetic models and pathological involvement of microglia.Developmental medicine and child neurology · 2025Review
- Ribonucleases in Mendelian disease: Characterization and insight from model organisms.Genes & diseases · 2025Review
- Regional and aging-specific cellular architecture of non-human primate brains.Genome medicine · 2025Article
- Second generation lethality in RNAseH2a knockout zebrafish.Nucleic acids research · 2024Article
- Macrophage transplantation rescues RNASET2-deficient leukodystrophy by replacing deficient microglia in a zebrafish model.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Preclinical Models for Cryptococcosis of the CNS and Their Characterization Using In Vivo Imaging Techniques.Journal of fungi (Basel, Switzerland) · 2024Review
- The Potential Role of the T2 Ribonucleases in TME-Based Cancer Therapy.Biomedicines · 2023Review
- Zebrafish as a Model Organism for Studying Pathologic Mechanisms of Neurodegenerative Diseases and other Neural Disorders.Cellular and molecular neurobiology · 2023Review
- Review
- Microglial debris is cleared by astrocytes via C4b-facilitated phagocytosis and degraded via RUBICON-dependent noncanonical autophagy in mice.Nature communications · 2022Article
- Long-term in vivo imaging of mouse spinal cord through an optically cleared intervertebral window.Nature communications · 2022Article
- A zebrafish reporter line reveals immune and neuronal expression of endogenous retrovirus.Disease models & mechanisms · 2022Article
- The Interplay Between Autophagy and RNA Homeostasis: Implications for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.Frontiers in cell and developmental biology · 2022Review
- The behavior and functions of embryonic microglia.Anatomical science international · 2022Review
- Epigenetics and Neuroinflammation Associated With Neurodevelopmental Disorders: A Microglial Perspective.Frontiers in cell and developmental biology · 2022Review
- Interferon-driven brain phenotype in a mouse model of RNaseT2 deficient leukoencephalopathy.Nature communications · 2021Article
- The multicellular interplay of microglia in health and disease: lessons from leukodystrophy.Disease models & mechanisms · 2021Review
- The effect of absent blood flow on the zebrafish cerebral and trunk vasculature.Vascular biology (Bristol, England) · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The contribution of microglia in neurological disorders is emerging as a leading disease driver rather than a consequence of pathology. RNAseT2-deficient leukoencephalopathy is a severe childhood white matter disorder affecting patients in their first year of life and mimicking a cytomegalovirus brain infection. The early onset and resemblance of the symptoms to a viral infection suggest an inflammatory and embryonic origin of the pathology. There are no treatments available for this disease as our understanding of the cellular drivers of the pathology are still unknown. In this study, using a zebrafish mutant for the orthologous rnaset2 gene, we have identified an inflammatory signature in early development and an antiviral immune response in mature adult brains. Using the optical transparency and the ex utero development of the zebrafish larvae we studied immune cell behavior during brain development and identified abnormal microglia as an early marker of pathology. Live imaging and electron microscopy identified that mutant microglia displayed an engorged morphology and were filled with undigested apoptotic cells and undigested substrate. Using microglia-specific depletion and rescue experiments, we identified microglia as drivers of this embryonic phenotype and potential key cellular player in the pathology of RNAseT2-deficient leukoencephalopathy. Our zebrafish model also presented with reduced survival and locomotor defects, therefore recapitulating many aspects of the human disease. Our study therefore placed our rnaset2 mutant at the forefront of leukodystrophy preclinical models and highlighted tissue-specific approaches as future therapeutic avenues.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.