The epg5 knockout zebrafish line: a model to study Vici syndrome

Autophagy
Giacomo MeneghettiLuisa Dalla Valle

Abstract

The EPG5 protein is a RAB7A effector involved in fusion specificity between autophagosomes and late endosomes or lysosomes during macroautophagy/autophagy. Mutations in the human EPG5 gene cause a rare and severe multisystem disorder called Vici syndrome. In this work, we show that zebrafish epg5-/- mutants from both heterozygous and incrossed homozygous matings are viable and can develop to the age of sexual maturity without conspicuous defects in external appearance. In agreement with the dysfunctional autophagy of Vici syndrome, western blot revealed higher levels of the Lc3-II autophagy marker in epg5-/- mutants with respect to wild type controls. Moreover, starvation elicited higher accumulation of Lc3-II in epg5-/- than in wild type larvae, together with a significant reduction of skeletal muscle birefringence. Accordingly, muscle ultrastructural analysis revealed accumulation of degradation-defective autolysosomes in starved epg5-/- mutants. By aging, epg5-/- mutants showed impaired motility and muscle thinning, together with accumulation of non-degradative autophagic vacuoles. Furthermore, epg5-/- adults displayed morphological alterations in gonads and heart. These findings point at the zebrafish epg5 mutant as a valua...Continue Reading

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Citations

Mar 7, 2020·Biotechnology Journal·Margarita-Elena Papandreou, Nektarios Tavernarakis
Sep 12, 2020·Histochemistry and Cell Biology·Joanna J MossJon D Lane
Mar 3, 2021·Experimental & Molecular Medicine·Tae-Young ChoiCheol-Hee Kim
Apr 4, 2021·Cells·Georgios Konstantinidis, Nektarios Tavernarakis

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Datasets Mentioned

BETA
MG775431
K270020

Methods Mentioned

BETA
PCR
genotyping
Transmission electron microscopy
transgenic
electron microscopy
fluorescence
electron
biopsies
electrophoresis
reverse transcription PCR

Software Mentioned

WMISH
NIS ELEMENTS
Poly
BLAST
Fiji ImageJ
crisp design
Ensembl
Peak Parser
TIS Miner
PolyPeakParser

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