Weber, T., Schlotawa, L., Dosch, R. et al. (6 more authors) (2020) Zebrafish disease model of human RNASET2-deficient cystic leukoencephalopathy displays abnormalities in early microglia. Biology Open, 9 (5). bio049239.
Abstract
Human infantile-onset RNASET2-deficient cystic leukoencephalopathy is a Mendelian mimic of in utero cytomegalovirus brain infection with prenatally developing inflammatory brain lesions. We used an RNASET2-deficient zebrafish model to elucidate the underlying disease mechanisms. Mutant and wild-type zebrafish larvae brain development between 2 and 5 days post fertilization (dpf) was examined by confocal live imaging in fluorescent reporter lines of the major types of brain cells. In contrast to wild-type brains, RNASET2-deficient larvae displayed increased numbers of microglia with altered morphology, often containing inclusions of neurons. Furthermore, lysosomes within distinct populations of the myeloid cell lineage including microglia showed increased lysosomal staining. Neurons and oligodendrocyte precursor cells remained unaffected. This study provides a first look into the prenatal onset pathomechanisms of human RNASET2-deficient leukoencephalopathy, linking this inborn lysosomal disease to the innate immune system and other immune-related childhood encephalopathies like Aicardi-Goutières syndrome (AGS).
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
Keywords: | Cystic leukoencephalopathy; Innate immune system; Zebrafish; Lysosomes; RNASET2 |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection and Immunity (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 01 Jun 2020 08:05 |
Last Modified: | 01 Jun 2020 08:05 |
Status: | Published |
Publisher: | The Company of Biologists |
Refereed: | Yes |
Identification Number: | 10.1242/bio.049239 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:161184 |