Highly efficient cell-type-specific gene inactivation reveals a key function for the Drosophila FUS homolog cabeza in neurons

Scientific Reports
Marie FrickenhausErik Storkebaum

Abstract

To expand the rich genetic toolkit of Drosophila melanogaster, we evaluated whether introducing FRT or LoxP sites in endogenous genes could allow for cell-type-specific gene inactivation in both dividing and postmitotic cells by GAL4-driven expression of FLP or Cre recombinase. For proof of principle, conditional alleles were generated for cabeza (caz), the Drosophila homolog of human FUS, a gene implicated in the neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Upon selective expression in neurons or muscle, both FLP and Cre mediated caz inactivation in all neurons or muscle cells, respectively. Neuron-selective caz inactivation resulted in failure of pharate adult flies to eclose from the pupal case, and adult escapers displayed motor performance defects and reduced life span. Due to Cre-toxicity, FLP/FRT is the preferred system for cell-type-specific gene inactivation, and this strategy outperforms RNAi-mediated knock-down. Furthermore, the GAL80 target system allowed for temporal control over gene inactivation, as induction of FLP expression from the adult stage onwards still inactivated caz in >99% of neurons. Remarkably, selective caz inactivation in adult neurons did not ...Continue Reading

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Citations

Nov 17, 2017·Scientific Reports·Luca Lo PiccoloMasamitsu Yamaguchi
Nov 30, 2016·RNA Biology·Svetlana LebedevaRené F Ketting
Sep 14, 2018·The Journal of Cell Biology·Moushami MallikErik Storkebaum
Oct 22, 2016·Genesis : the Journal of Genetics and Development·Qingxiang ZhouFrancesca Pignoni
Oct 30, 2016·RNA Biology·Francesca SvetoniMaria Paola Paronetto
Dec 16, 2018·Development·Anna F GillesMichalis Averof
Apr 28, 2016·Scientific Reports·Martine TherrienJ Alex Parker
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Jan 23, 2021·International Journal of Molecular Sciences·Sophie LayalleLaurent Soustelle
May 8, 2020·Neurobiology of Disease·Annis-Rayan BourefisEdor Kabashi
Apr 5, 2021·Experimental Cell Research·Masamitsu YamaguchiHideki Yoshida
Apr 6, 2021·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Brecht DriesschaertLiesbet Temmerman
Jul 30, 2021·Cellular and Molecular Life Sciences : CMLS·Francesco LiguoriCinzia Volonté

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Methods Mentioned

BETA
transgenic
gene knock-out
PCR
genotyping
dissection

Software Mentioned

Excel
MTrack3
GraphPad Prism
FIJI
ImageJ

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