Adult mouse eIF2Bε Arg191His astrocytes display a normal integrated stress response in vitro

Scientific Reports
Lisanne E WisseTruus E M Abbink

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 detec...Continue Reading

References

Oct 1, 1988·Annals of Neurology·D N BlackE Reece
Dec 1, 1996·Journal of Neurochemistry·H Wei, D C Perry
Apr 1, 1997·Neurology·M S van der KnaapJ Valk
Sep 29, 2001·Progress in Molecular and Subcellular Biology·C G Proud
Sep 27, 2002·Annals of Neurology·Anne FogliRaphael Schiffmann
Oct 16, 2003·Molecular and Cellular Biology·Ann-Hwee LeeLaurie H Glimcher
Jun 26, 2004·Journal of Neuropathology and Experimental Neurology·Keith Van HarenJames M Powers
Jan 22, 2005·Seminars in Cell & Developmental Biology·Christopher G Proud
Feb 22, 2005·Nature Medicine·Jörg DietrichChristoph Pröschel
Sep 6, 2005·Journal of Neuropathology and Experimental Neurology·J Patrick van der VoornMarjo S van der Knaap
Sep 28, 2005·Neurobiology of Disease·Barbara van KollenburgGert C Scheper
Apr 25, 2006·Lancet Neurology·Marjo S van der KnaapGert C Scheper
Jun 14, 2006·Proceedings of the National Academy of Sciences of the United States of America·Daniela C DieterichErin M Schuman
Jul 11, 2006·Journal of Neuropathology and Experimental Neurology·Barbara van KollenburgMarjo S van der Knaap
Dec 11, 2008·The Journal of Pharmacology and Experimental Therapeutics·Wenxian HuStephen G Swisher
Nov 11, 2010·Gene Expression·Yin HeLing Qi
Dec 16, 2010·Journal of Neuropathology and Experimental Neurology·Marianna BugianiMarjo S van der Knaap
Jul 19, 2011·Nature Chemical Biology·Ting ChenBertal H Aktas
Feb 14, 2012·Nature Chemical Biology·Tracy L KellerMalcolm Whitman
Jun 4, 2014·PloS One·Christiane NeuberThomas Eschenhagen
Aug 13, 2014·Molecular and Cellular Biology·Gordon P MearesEtty N Benveniste
Mar 15, 2016·The Journal of Clinical Investigation·Stephanie DoovesMarjo S van der Knaap
Sep 16, 2016·EMBO Reports·Karolina Pakos-ZebruckaAdrienne M Gorman
Sep 17, 2016·Scientific Reports·Shusuke TaniuchiSeiichi Oyadomari
Jan 30, 2018·Frontiers in Cellular Neuroscience·Lisanne E WisseTruus E M Abbink

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Citations

Aug 14, 2019·Annals of Clinical and Translational Neurology·Truus E M AbbinkMarjo S van der Knaap

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Methods Mentioned

BETA
nucleotide exchange

Software Mentioned

UNIANOVA
Factor

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