Interferon-driven brain phenotype in a mouse model of RNaseT2 deficient leukoencephalopathy
2021 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Interferon-driven brain phenotype in a mouse model of RNaseT2 deficient leukoencephalopathy
Kettwig, M.; Ternka, K.; Wendland, K.; Krüger, D. M.; Zampar, S.; Schob, C. & Franz, J. et al. (2021)
Nature Communications, 12(1) art. 6530. DOI: https://doi.org/10.1038/s41467-021-26880-x
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Details
- Authors
- Kettwig, Matthias; Ternka, Katharina; Wendland, Kristin; Krüger, Dennis Manfred; Zampar, Silvia; Schob, Charlotte; Franz, Jonas; Aich, Abhishek ; Winkler, Anne ; Sakib, M. Sadman; Gärtner, Jutta
- Abstract
- Abstract Infantile-onset RNaseT2 deficient leukoencephalopathy is characterised by cystic brain lesions, multifocal white matter alterations, cerebral atrophy, and severe psychomotor impairment. The phenotype is similar to congenital cytomegalovirus brain infection and overlaps with type I interferonopathies, suggesting a role for innate immunity in its pathophysiology. To date, pathophysiological studies have been hindered by the lack of mouse models recapitulating the neuroinflammatory encephalopathy found in patients. In this study, we generated Rnaset2 −/− mice using CRISPR/Cas9-mediated genome editing. Rnaset2 −/− mice demonstrate upregulation of interferon-stimulated genes and concurrent IFNAR1-dependent neuroinflammation, with infiltration of CD8 + effector memory T cells and inflammatory monocytes into the grey and white matter. Single nuclei RNA sequencing reveals homeostatic dysfunctions in glial cells and neurons and provide important insights into the mechanisms of hippocampal-accentuated brain atrophy and cognitive impairment. The Rnaset2 −/− mice may allow the study of CNS damage associated with RNaseT2 deficiency and may be used for the investigation of potential therapies.
- Issue Date
- 2021
- Journal
- Nature Communications
- Project
- EXC 2067: Multiscale Bioimaging
TRR 274: Checkpoints of Central Nervous System Recovery
SFB 1286: Quantitative Synaptologie
SFB 1286 | B06: Die Rolle von RNA in Synapsenphysiologie und Neurodegeneration - Working Group
- RG A. Fischer (Epigenetics and Systems Medicine in Neurodegenerative Diseases)
RG Gärtner
RG Rehling (Mitochondrial Protein Biogenesis)
RG Stadelmann-Nessler - eISSN
- 2041-1723
- Language
- English