Characterization of a Drosophila model for Chorea‐Acanthocytosis

Jan Vonk

Characterization of a Drosophila model for Chorea‐Acanthocytosis

Vertaalde titel van de bijdrage: Karakterisatie van een Drosophila model voor Chorea-Acanthocytose

Jan Vonk

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Chorea-Acanthocytose is een zeldzame hersenziekte die leidt tot achteruitgang van hersenfunctie en bewegingsstoornissen. Het wordt veroorzaakt door dysfunctie van het VPS13A gen. Hoe VPS13A dysfunctie leidt tot Chorea-Acanthocytose is nog niet bekend.
Het doel van dit project was om de fysiologische rol van VPS13A te onderzoeken door gebruik te maken van de fruitvlieg, Drosophila melanogaster, als model organisme. De fruitvlieg heeft een gen, genaamd Vps13, wat veel lijkt op het humane VPS13A gen. Onze resultaten laten zien dat Vps13 dysfunctie leidt tot een kortere levensduur van de vliegen en functionele achteruitgang in het centraal zenuwstelsel. Daarnaast speelt Vps13 ook een rol in het behouden van een goede eiwit homeostase in het centraal zenuwstelsel. Veel neurodegeneratieve hersenziekten worden gekenmerkt door een defect in eiwit homeostase in het centraal zenuwstelsel, maar voor Chorea-Acanthocytose is dit nog niet bekend. Onze resultaten laten ook zien dat het humane VPS13A gen gedeeltelijk kan compenseren voor Vps13 dysfunctie. Dit betekend dat humaan VPS13A en Drosophila Vps13 overlappende functies hebben.
Dit onderzoek laat zien dat het Drosophila model gebruikt kan worden om Vps13 functie in de fysiologie van een organisme te bestuderen. Hiernaast kan het model informatie geven over de mogelijke pathologische oorzaken van Chorea-Acanthocytose en kan het gebruikt worden om potentiele therapeutische strategieën te ontwikkelen.

Vertaalde titel van de bijdrage	Karakterisatie van een Drosophila model voor Chorea-Acanthocytose
Originele taal-2	English
Kwalificatie	Doctor of Philosophy
Toekennende instantie	Rijksuniversiteit Groningen
Begeleider(s)/adviseur	Sibon, Ody, Supervisor
Datum van toekenning	3-jul.-2017
Plaats van publicatie	[Groningen]
Uitgever	University of Groningen
Gedrukte ISBN's	978-90-367-9868-6
Elektronische ISBN's	978-90-367-9867-9
Status	Published - 2017

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Title and contentsFinal publisher's version, 84,3 KB
Chapter 1Final publisher's version, 167 KB
Chapter 2Final publisher's version, 1,21 MB
Chapter 3Final publisher's version, 9,77 MB
Chapter 4Final publisher's version, 7,03 MB
Chapter 5Final publisher's version, 297 KB
AppendicesFinal publisher's version, 91,5 KB
Complete thesisFinal publisher's version, 18,1 MB
PropositionsFinal publisher's version, 76,6 KB

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title = "Characterization of a Drosophila model for Chorea‐Acanthocytosis",

abstract = "Chorea-Acanthocytosis is a rare neurodegenerative disorder which leads to degeneration in the central nervous system and movement disorders. It is caused by dysfunction of the VPS13A gene. How VPS13A dysfunction leads to Chorea-Acanthocytosis is not known.The goal of this project was to investigate the physiological role of VPS13A by using the common fruit fly, Drosophila melanogaster, as a model organism. The fruit fly contains a gene very similar to human VPS13A which is called Vps13. Our results show that dysfunction of Vps13 in the fruit fly leads to a decreased life span and neurodegeneration. Additionally, the Vps13 gene is required for maintaining protein homeostasis in the fruit fly central nervous system. Many neurodegenerative disorders are characterized by defects in protein homeostasis, however for Chorea-Acanthocytosis this is not yet known. When we introduced the human VPS13A in our Vps13 dysfunctional fruit flies it rescued some of the phenotypes, among which the shortened life span and the protein homeostasis dysfunction. This result shows that the human gene can partly take over the function of the fruit fly Vps13 and that human VPS13A and Drosophila Vps13 have overlapping functions.The Drosophila model we established can be used to study the function of Vps13 in the physiology of an organism. It may also give insight in the causes of Chorea-Acanthocytosis and provide a way to develop possible therapeutic strategies.",

author = "Jan Vonk",

year = "2017",

language = "English",

isbn = "978-90-367-9868-6",

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TY - BOOK

T1 - Characterization of a Drosophila model for Chorea‐Acanthocytosis

AU - Vonk, Jan

PY - 2017

Y1 - 2017

N2 - Chorea-Acanthocytosis is a rare neurodegenerative disorder which leads to degeneration in the central nervous system and movement disorders. It is caused by dysfunction of the VPS13A gene. How VPS13A dysfunction leads to Chorea-Acanthocytosis is not known.The goal of this project was to investigate the physiological role of VPS13A by using the common fruit fly, Drosophila melanogaster, as a model organism. The fruit fly contains a gene very similar to human VPS13A which is called Vps13. Our results show that dysfunction of Vps13 in the fruit fly leads to a decreased life span and neurodegeneration. Additionally, the Vps13 gene is required for maintaining protein homeostasis in the fruit fly central nervous system. Many neurodegenerative disorders are characterized by defects in protein homeostasis, however for Chorea-Acanthocytosis this is not yet known. When we introduced the human VPS13A in our Vps13 dysfunctional fruit flies it rescued some of the phenotypes, among which the shortened life span and the protein homeostasis dysfunction. This result shows that the human gene can partly take over the function of the fruit fly Vps13 and that human VPS13A and Drosophila Vps13 have overlapping functions.The Drosophila model we established can be used to study the function of Vps13 in the physiology of an organism. It may also give insight in the causes of Chorea-Acanthocytosis and provide a way to develop possible therapeutic strategies.

AB - Chorea-Acanthocytosis is a rare neurodegenerative disorder which leads to degeneration in the central nervous system and movement disorders. It is caused by dysfunction of the VPS13A gene. How VPS13A dysfunction leads to Chorea-Acanthocytosis is not known.The goal of this project was to investigate the physiological role of VPS13A by using the common fruit fly, Drosophila melanogaster, as a model organism. The fruit fly contains a gene very similar to human VPS13A which is called Vps13. Our results show that dysfunction of Vps13 in the fruit fly leads to a decreased life span and neurodegeneration. Additionally, the Vps13 gene is required for maintaining protein homeostasis in the fruit fly central nervous system. Many neurodegenerative disorders are characterized by defects in protein homeostasis, however for Chorea-Acanthocytosis this is not yet known. When we introduced the human VPS13A in our Vps13 dysfunctional fruit flies it rescued some of the phenotypes, among which the shortened life span and the protein homeostasis dysfunction. This result shows that the human gene can partly take over the function of the fruit fly Vps13 and that human VPS13A and Drosophila Vps13 have overlapping functions.The Drosophila model we established can be used to study the function of Vps13 in the physiology of an organism. It may also give insight in the causes of Chorea-Acanthocytosis and provide a way to develop possible therapeutic strategies.

M3 - Thesis fully internal (DIV)

SN - 978-90-367-9868-6

PB - University of Groningen

CY - [Groningen]

ER -

Characterization of a Drosophila model for Chorea‐Acanthocytosis

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