wobbler mouse
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2021 ◽  
Vol 12 ◽  
Author(s):  
Emily C. Wilkinson ◽  
Emily L. Starke ◽  
Scott A. Barbee

Vps54 is an integral subunit of the Golgi-associated retrograde protein (GARP) complex, which is involved in tethering endosome-derived vesicles to the trans-Golgi network (TGN). A destabilizing missense mutation in Vps54 causes the age-progressive motor neuron (MN) degeneration, muscle weakness, and muscle atrophy observed in the wobbler mouse, an established animal model for human MN disease. It is currently unclear how the disruption of Vps54, and thereby the GARP complex, leads to MN and muscle phenotypes. To develop a new tool to address this question, we have created an analogous model in Drosophila by generating novel loss-of-function alleles of the fly Vps54 ortholog (scattered/scat). We find that null scat mutant adults are viable but have a significantly shortened lifespan. Like phenotypes observed in the wobbler mouse, we show that scat mutant adults are male sterile and have significantly reduced body size and muscle area. Moreover, we demonstrate that scat mutant adults have significant age-progressive defects in locomotor function. Interestingly, we see sexually dimorphic effects, with scat mutant adult females exhibiting significantly stronger phenotypes. Finally, we show that scat interacts genetically with rab11 in MNs to control age-progressive muscle atrophy in adults. Together, these data suggest that scat mutant flies share mutant phenotypes with the wobbler mouse and may serve as a new genetic model system to study the cellular and molecular mechanisms underlying MN disease.


2021 ◽  
Author(s):  
Emily C Wilkinson ◽  
Emily L Starke ◽  
Scott A Barbee

Vps54 is an integral subunit of the Golgi-associated retrograde protein (GARP) complex, which is involved in tethering endosome-derived vesicles to the trans-Golgi network (TGN). A destabilizing missense mutation in Vps54 causes the age-progressive motor neuron (MN) degeneration, muscle weakness, and muscle atrophy observed in the wobbler mouse, an established animal model for human MN disease. It is currently unclear how the disruption of Vps54, and thereby the GARP complex, leads to MN and muscle phenotypes. To develop a new tool to address this question, we have created an analogous model in Drosophila by generating novel loss-of-function alleles of the fly Vps54 ortholog (scattered/scat). We find that null scat mutant adults are viable but have a significantly shortened lifespan. Like phenotypes observed in the wobbler mouse, we show that scat mutant adults are male sterile and have significantly reduced body size and muscle area. Moreover, we demonstrate that scat mutant adults have significant age-progressive defects in locomotor function. Interestingly, we see sexually dimorphic effects, with scat mutant adult females exhibiting significantly stronger phenotypes. Finally, we show that scat interacts genetically with rab11 in MNs to control age-progressive muscle atrophy in adults. Together, these data suggest that scat mutant flies share mutant phenotypes with the wobbler mouse and may serve as a new genetic model system to study the cellular and molecular mechanisms underlying MN disease.


Author(s):  
Agustina Lara ◽  
Iván Esperante ◽  
Maria Meyer ◽  
Philippe Liere ◽  
Noelia Di Giorgio ◽  
...  

2017 ◽  
Vol 658 ◽  
pp. 85-90 ◽  
Author(s):  
Signe Rode Andreasen ◽  
Camilla Johanne Lundbye ◽  
Tine Breckling Christensen ◽  
Karina Dvinge Thielsen ◽  
Thomas Schmitt-John ◽  
...  

2017 ◽  
Vol 03 (01) ◽  
Author(s):  
Bastian Ott ◽  
Carolin Dahlke ◽  
Darius Saberi ◽  
Beate Brand-Saberi ◽  
Veronika Matschke ◽  
...  

Endocrinology ◽  
2016 ◽  
Vol 157 (11) ◽  
pp. 4446-4460 ◽  
Author(s):  
Maria Claudia Gonzalez Deniselle ◽  
Philippe Liere ◽  
Antoine Pianos ◽  
Maria Meyer ◽  
Fanny Aprahamian ◽  
...  

2016 ◽  
Vol 75 (4) ◽  
pp. 347-357 ◽  
Author(s):  
Darius Saberi ◽  
Bastian Ott ◽  
Carolin Dahlke ◽  
Veronika Matschke ◽  
Thomas Schmitt-John ◽  
...  

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