Generation and Characterization of the Drosophila melanogaster paralytic Gene Knock-Out as a Model for Dravet Syndrome

Dravet syndrome is a severe rare epileptic disease caused by mutations in the SCN1A gene coding for the Nav1.1 protein, a voltage-gated sodium channel alpha subunit. We have made a knock-out of the paralytic gene, the single Drosophila melanogaster</...

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Autores principales:	Andrea Tapia, Carlo N. Giachello, Martina Palomino-Schätzlein, Richard A. Baines, Máximo Ibo Galindo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Dravet syndrome epilepsy voltage-gated sodium channel gabaergic neurons electrophysiology metabolomics Science Q
Acceso en línea:	https://doaj.org/article/1f156631eefa4c33926b88474ef18544
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spelling	oai:doaj.org-article:1f156631eefa4c33926b88474ef185442021-11-25T18:11:39ZGeneration and Characterization of the <i>Drosophila melanogaster paralytic</i> Gene Knock-Out as a Model for Dravet Syndrome10.3390/life111112612075-1729https://doaj.org/article/1f156631eefa4c33926b88474ef185442021-11-01T00:00:00Zhttps://www.mdpi.com/2075-1729/11/11/1261https://doaj.org/toc/2075-1729Dravet syndrome is a severe rare epileptic disease caused by mutations in the <i>SCN1A</i> gene coding for the Nav1.1 protein, a voltage-gated sodium channel alpha subunit. We have made a knock-out of the <i>paralytic</i> gene, the single <i>Drosophila melanogaster</i> gene encoding this type of protein, by homologous recombination. These flies showed a heat-induced seizing phenotype, and sudden death in long term seizures. In addition to seizures, neuromuscular alterations were observed in climbing, flight, and walking tests. Moreover, they also manifested some cognitive alterations, such as anxiety and problems in learning. Electrophysiological analyses from larval motor neurons showed a decrease in cell capacitance and membrane excitability, while persistent sodium current increased. To detect alterations in metabolism, we performed an NMR metabolomic profiling of heads, which revealed higher levels in some amino acids, succinate, and lactate; and also an increase in the abundance of GABA, which is the main neurotransmitter implicated in Dravet syndrome. All these changes in the <i>paralytic</i> knock-out flies indicate that this is a good model for epilepsy and specifically for Dravet syndrome. This model could be a new tool to understand the pathophysiology of the disease and to find biomarkers, genetic modifiers and new treatments.Andrea TapiaCarlo N. GiachelloMartina Palomino-SchätzleinRichard A. BainesMáximo Ibo GalindoMDPI AGarticleDravet syndromeepilepsyvoltage-gated sodium channelgabaergic neuronselectrophysiologymetabolomicsScienceQENLife, Vol 11, Iss 1261, p 1261 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Dravet syndrome epilepsy voltage-gated sodium channel gabaergic neurons electrophysiology metabolomics Science Q
spellingShingle	Dravet syndrome epilepsy voltage-gated sodium channel gabaergic neurons electrophysiology metabolomics Science Q Andrea Tapia Carlo N. Giachello Martina Palomino-Schätzlein Richard A. Baines Máximo Ibo Galindo Generation and Characterization of the <i>Drosophila melanogaster paralytic</i> Gene Knock-Out as a Model for Dravet Syndrome
description	Dravet syndrome is a severe rare epileptic disease caused by mutations in the <i>SCN1A</i> gene coding for the Nav1.1 protein, a voltage-gated sodium channel alpha subunit. We have made a knock-out of the <i>paralytic</i> gene, the single <i>Drosophila melanogaster</i> gene encoding this type of protein, by homologous recombination. These flies showed a heat-induced seizing phenotype, and sudden death in long term seizures. In addition to seizures, neuromuscular alterations were observed in climbing, flight, and walking tests. Moreover, they also manifested some cognitive alterations, such as anxiety and problems in learning. Electrophysiological analyses from larval motor neurons showed a decrease in cell capacitance and membrane excitability, while persistent sodium current increased. To detect alterations in metabolism, we performed an NMR metabolomic profiling of heads, which revealed higher levels in some amino acids, succinate, and lactate; and also an increase in the abundance of GABA, which is the main neurotransmitter implicated in Dravet syndrome. All these changes in the <i>paralytic</i> knock-out flies indicate that this is a good model for epilepsy and specifically for Dravet syndrome. This model could be a new tool to understand the pathophysiology of the disease and to find biomarkers, genetic modifiers and new treatments.
format	article
author	Andrea Tapia Carlo N. Giachello Martina Palomino-Schätzlein Richard A. Baines Máximo Ibo Galindo
author_facet	Andrea Tapia Carlo N. Giachello Martina Palomino-Schätzlein Richard A. Baines Máximo Ibo Galindo
author_sort	Andrea Tapia
title	Generation and Characterization of the <i>Drosophila melanogaster paralytic</i> Gene Knock-Out as a Model for Dravet Syndrome
title_short	Generation and Characterization of the <i>Drosophila melanogaster paralytic</i> Gene Knock-Out as a Model for Dravet Syndrome
title_full	Generation and Characterization of the <i>Drosophila melanogaster paralytic</i> Gene Knock-Out as a Model for Dravet Syndrome
title_fullStr	Generation and Characterization of the <i>Drosophila melanogaster paralytic</i> Gene Knock-Out as a Model for Dravet Syndrome
title_full_unstemmed	Generation and Characterization of the <i>Drosophila melanogaster paralytic</i> Gene Knock-Out as a Model for Dravet Syndrome
title_sort	generation and characterization of the <i>drosophila melanogaster paralytic</i> gene knock-out as a model for dravet syndrome
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1f156631eefa4c33926b88474ef18544
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Generation and Characterization of the <i>Drosophila melanogaster paralytic</i> Gene Knock-Out as a Model for Dravet Syndrome

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