163450 20240302115204.0 10.1038/s41467-021-26880-x doi pmid:34764281 pmid pmc:PMC8586222 pmc altmetric:116626305 altmetric DZNE-2022-00210 English 500 Kettwig, Matthias 0000-0003-4804-7716 0 Interferon-driven brain phenotype in a mouse model of RNaseT2 deficient leukoencephalopathy. [London] 2021 Nature Publishing Group UK article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1709309565_5353 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote (CC BY) 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. 352 - Disease Mechanisms (POF4-352) G:(DE-HGF)POF4-352 POF4-352 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Endoribonucleases EC 3.1.- NLM Chemicals Animals MeSH CD8-Positive T-Lymphocytes: metabolism MeSH Cognitive Dysfunction: genetics MeSH Cognitive Dysfunction: metabolism MeSH Disease Models, Animal MeSH Endoribonucleases: genetics MeSH Endoribonucleases: metabolism MeSH Female MeSH Flow Cytometry MeSH Genotype MeSH Humans MeSH Immunohistochemistry MeSH Leukoencephalopathies: genetics MeSH Leukoencephalopathies: metabolism MeSH Leukoencephalopathies: pathology MeSH Magnetic Resonance Imaging MeSH Male MeSH Memory T Cells: metabolism MeSH Mice MeSH Mice, Knockout MeSH Neuroglia: metabolism MeSH Real-Time Polymerase Chain Reaction MeSH Ternka, Katharina 0000-0003-3773-4625 1 Wendland, Kristin 2 Krüger, Dennis Manfred P:(DE-2719)2812548 3 dzne Zampar, Silvia 0000-0003-0134-0974 4 Schob, Charlotte 5 Franz, Jonas 0000-0001-7523-6622 6 Aich, Abhishek 0000-0001-8331-9874 7 Winkler, Anne 8 Sakib, M Sadman P:(DE-2719)2812054 9 dzne Kaurani, Lalit P:(DE-2719)2812832 10 dzne Epple, Robert P:(DE-2719)2812061 11 dzne Werner, Hauke B 0000-0002-7710-5738 12 Hakroush, Samy 13 Kitz, Julia 14 Prinz, Marco 0000-0002-0349-1955 15 Bartok, Eva 0000-0003-0556-1950 16 Hartmann, Gunther 17 Schröder, Simone 18 Rehling, Peter 19 Henneke, Marco 20 Boretius, Susann 0000-0003-2792-7423 21 Alia, A. 22 Wirths, Oliver 0000-0002-4115-0334 23 Fischer, Andre P:(DE-2719)2000047 24 dzne Stadelmann, Christine P:(DE-2719)9000922 25 dzne Nessler, Stefan 26 Gärtner, Jutta P:(DE-2719)2811933 27 dzne 10.1038/s41467-021-26880-x Vol. 12, no. 1, p. 6530 PERI:(DE-600)2553671-0 1 6530 Nature Communications 12 2021 2041-1723 http://pub.dzne.de/record/163450/files/DZNE-2022-00210.pdf OpenAccess http://pub.dzne.de/record/163450/files/DZNE-2022-00210.pdf?subformat=pdfa pdfa OpenAccess oai:pub.dzne.de:163450 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)2812548 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 9 P:(DE-2719)2812054 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 10 P:(DE-2719)2812832 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 11 P:(DE-2719)2812061 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 24 P:(DE-2719)2000047 External Institute I:(DE-HGF)0 Extern 25 P:(DE-2719)9000922 External Institute I:(DE-HGF)0 Extern 27 P:(DE-2719)2811933 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-352 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Disease Mechanisms 0 2021 Article Processing Charges StatID:(DE-HGF)0561 StatID 2021-02-02 Creative Commons Attribution CC BY (No Version) LIC:(DE-HGF)CCBYNV V:(DE-HGF) DOAJ 2021-02-02 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2021-02-02 Fees StatID:(DE-HGF)0700 StatID 2021-02-02 OpenAccess StatID:(DE-HGF)0510 StatID DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2021-02-02 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2021-02-02 JCR StatID:(DE-HGF)0100 StatID NAT COMMUN : 2021 2022-11-11 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-11 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-11 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2021-10-13T14:44:21Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2021-10-13T14:44:21Z Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Peer review 2021-10-13T14:44:21Z DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-11 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-11 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-11 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2022-11-11 DBCoverage StatID:(DE-HGF)1040 StatID Zoological Record 2022-11-11 DBCoverage StatID:(DE-HGF)1060 StatID Current Contents - Agriculture, Biology and Environmental Sciences 2022-11-11 DBCoverage StatID:(DE-HGF)1150 StatID Current Contents - Physical, Chemical and Earth Sciences 2022-11-11 IF >= 15 StatID:(DE-HGF)9915 StatID NAT COMMUN : 2021 2022-11-11 I:(DE-2719)1440016 Bioinformatics and Genome Dynamics Core Bioinformatics and Genome Dynamics Core 0 I:(DE-2719)1410002 AG Fischer Epigenetics and Systems Medicine in Neurodegenerative Diseases 1 journal VDB I:(DE-2719)1440016 I:(DE-2719)1410002 UNRESTRICTED FullTexts