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Type: Journal article
Title: Adult mouse eIF2Bϵ Arg191His astrocytes display a normal integrated stress response in vitro
Other Titles: Adult mouse eIF2Bepsilon Arg191His astrocytes display a normal integrated stress response in vitro
Author: Wisse, L.
Ter Braak, T.
Van De Beek, M.
Van Berkel, C.
Wortel, J.
Heine, V.
Proud, C.
Van Der Knaap, M.
Abbink, T.
Citation: Scientific Reports, 2018; 8(1):3773-3773
Publisher: Nature
Issue Date: 2018
ISSN: 2045-2322
Statement of
Lisanne E. Wisse, Timo J. terBraak, Malu-Clair van de Beek, Carola G. M. van Berkel, Joke Wortel, Vivi M. Heine ... et al.
Abstract: Vanishing white matter (VWM) is a genetic childhood white matter disorder, characterized by chronic as well as episodic, stress provoked, neurological deterioration. Treatment is unavailable and patients often die within a few years after onset. VWM is caused by recessive mutations in the eukaryotic initiation factor 2B (eIF2B). eIF2B regulates protein synthesis rates in every cell of the body. In normal cells, various types of cellular stress inhibit eIF2B activity and induce the integrated stress response (ISR). We have developed a VWM mouse model homozygous for the pathogenic Arg191His mutation in eIF2Bε (2b5 ho ), representative of the human disease. Neuropathological examination of VWM patient and mouse brain tissue suggests that astrocytes are primarily affected. We hypothesized that VWM astrocytes are selectively hypersensitive to ISR induction, resulting in a heightened response. We cultured astrocytes from wildtype and VWM mice and investigated the ISR in assays that measure transcriptional induction of stress genes, protein synthesis rates and cell viability. We investigated the effects of short- and long-term stress as well as stress recovery. We detected congruent results amongst the various assays and did not detect a hyperactive ISR in VWM mouse astrocytes.
Keywords: Brain
Cells, Cultured
Mice, Knockout
Disease Models, Animal
Eukaryotic Initiation Factor-2B
Stress, Physiological
Unfolded Protein Response
In Vitro Techniques
Rights: © Te Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
DOI: 10.1038/s41598-018-21885-x
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Appears in Collections:Aurora harvest 4
Environment Institute publications

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