Home > Research > Publications & Outputs > Muscle strength deficiency and mitochondria...

Electronic data

  • DMM-2018-036137v2-Vanapalli

    Accepted author manuscript, 8.56 MB, PDF document

    Available under license: CC BY: Creative Commons Attribution 4.0 International License

Links

Text available via DOI:

View graph of relations

Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of C. elegans and its functional response to drugs

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Published

Standard

Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of C. elegans and its functional response to drugs. / Hewitt, Jennifer; Pollard, Amelia; Lesanpezeshki, Leila et al.

In: Disease Models & Mechanisms, Vol. 11, No. 11, 36137, 31.12.2018.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Hewitt, J, Pollard, A, Lesanpezeshki, L, Deane, C, Gaffney, CJ, Etheridge, T, Szewczyk, N & Vanapalli, S 2018, 'Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of C. elegans and its functional response to drugs', Disease Models & Mechanisms, vol. 11, no. 11, 36137. https://doi.org/10.1242/dmm.036137

APA

Hewitt, J., Pollard, A., Lesanpezeshki, L., Deane, C., Gaffney, C. J., Etheridge, T., Szewczyk, N., & Vanapalli, S. (2018). Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of C. elegans and its functional response to drugs. Disease Models & Mechanisms, 11(11), [36137]. https://doi.org/10.1242/dmm.036137

Vancouver

Hewitt J, Pollard A, Lesanpezeshki L, Deane C, Gaffney CJ, Etheridge T et al. Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of C. elegans and its functional response to drugs. Disease Models & Mechanisms. 2018 Dec 31;11(11):36137. Epub 2018 Dec 4. doi: 10.1242/dmm.036137

Author

Hewitt, Jennifer ; Pollard, Amelia ; Lesanpezeshki, Leila et al. / Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of C. elegans and its functional response to drugs. In: Disease Models & Mechanisms. 2018 ; Vol. 11, No. 11.

Bibtex

@article{2c9e9b97e8b6410ba7415cf9584d486e,
title = "Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of C. elegans and its functional response to drugs",
abstract = "Muscle strength is a key clinical parameter used to monitor the progression of human muscular dystrophies, including Duchenne and Becker muscular dystrophies. Although Caenorhabditis elegans is an established genetic model for studying the mechanisms and treatments of muscular dystrophies, analogous strength-based measurements in this disease model are lacking. Here, we describe the first demonstration of the direct measurement of muscular strength in dystrophin-deficient C. elegans mutants using a micropillar-based force measurement system called NemaFlex. We show that dys-1(eg33) mutants, but not dys-1(cx18) mutants, are significantly weaker than their wild-type counterparts in early adulthood, cannot thrash in liquid at wild-type rates, display mitochondrial network fragmentation in the body wall muscles, and have an abnormally high baseline mitochondrial respiration. Furthermore, treatment with prednisone, the standard treatment for muscular dystrophy in humans, and melatonin both improve muscular strength, thrashing rate and mitochondrial network integrity in dys-1(eg33), and prednisone treatment also returns baseline respiration to normal levels. Thus, our results demonstrate that the dys-1(eg33) strain is more clinically relevant than dys-1(cx18) for muscular dystrophy studies in C. elegans. This finding, in combination with the novel NemaFlex platform, can be used as an efficient workflow for identifying candidate compounds that can improve strength in the C. elegans muscular dystrophy model. Our study also lays the foundation for further probing of the mechanism of muscle function loss in dystrophin-deficient C. elegans, leading to knowledge translatable to human muscular dystrophy.",
author = "Jennifer Hewitt and Amelia Pollard and Leila Lesanpezeshki and Colleen Deane and Gaffney, {Christopher James} and Timothy Etheridge and Nathaniel Szewczyk and Siva Vanapalli",
year = "2018",
month = dec,
day = "31",
doi = "10.1242/dmm.036137",
language = "English",
volume = "11",
journal = "Disease Models & Mechanisms",
number = "11",

}

RIS

TY - JOUR

T1 - Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of C. elegans and its functional response to drugs

AU - Hewitt, Jennifer

AU - Pollard, Amelia

AU - Lesanpezeshki, Leila

AU - Deane, Colleen

AU - Gaffney, Christopher James

AU - Etheridge, Timothy

AU - Szewczyk, Nathaniel

AU - Vanapalli, Siva

PY - 2018/12/31

Y1 - 2018/12/31

N2 - Muscle strength is a key clinical parameter used to monitor the progression of human muscular dystrophies, including Duchenne and Becker muscular dystrophies. Although Caenorhabditis elegans is an established genetic model for studying the mechanisms and treatments of muscular dystrophies, analogous strength-based measurements in this disease model are lacking. Here, we describe the first demonstration of the direct measurement of muscular strength in dystrophin-deficient C. elegans mutants using a micropillar-based force measurement system called NemaFlex. We show that dys-1(eg33) mutants, but not dys-1(cx18) mutants, are significantly weaker than their wild-type counterparts in early adulthood, cannot thrash in liquid at wild-type rates, display mitochondrial network fragmentation in the body wall muscles, and have an abnormally high baseline mitochondrial respiration. Furthermore, treatment with prednisone, the standard treatment for muscular dystrophy in humans, and melatonin both improve muscular strength, thrashing rate and mitochondrial network integrity in dys-1(eg33), and prednisone treatment also returns baseline respiration to normal levels. Thus, our results demonstrate that the dys-1(eg33) strain is more clinically relevant than dys-1(cx18) for muscular dystrophy studies in C. elegans. This finding, in combination with the novel NemaFlex platform, can be used as an efficient workflow for identifying candidate compounds that can improve strength in the C. elegans muscular dystrophy model. Our study also lays the foundation for further probing of the mechanism of muscle function loss in dystrophin-deficient C. elegans, leading to knowledge translatable to human muscular dystrophy.

AB - Muscle strength is a key clinical parameter used to monitor the progression of human muscular dystrophies, including Duchenne and Becker muscular dystrophies. Although Caenorhabditis elegans is an established genetic model for studying the mechanisms and treatments of muscular dystrophies, analogous strength-based measurements in this disease model are lacking. Here, we describe the first demonstration of the direct measurement of muscular strength in dystrophin-deficient C. elegans mutants using a micropillar-based force measurement system called NemaFlex. We show that dys-1(eg33) mutants, but not dys-1(cx18) mutants, are significantly weaker than their wild-type counterparts in early adulthood, cannot thrash in liquid at wild-type rates, display mitochondrial network fragmentation in the body wall muscles, and have an abnormally high baseline mitochondrial respiration. Furthermore, treatment with prednisone, the standard treatment for muscular dystrophy in humans, and melatonin both improve muscular strength, thrashing rate and mitochondrial network integrity in dys-1(eg33), and prednisone treatment also returns baseline respiration to normal levels. Thus, our results demonstrate that the dys-1(eg33) strain is more clinically relevant than dys-1(cx18) for muscular dystrophy studies in C. elegans. This finding, in combination with the novel NemaFlex platform, can be used as an efficient workflow for identifying candidate compounds that can improve strength in the C. elegans muscular dystrophy model. Our study also lays the foundation for further probing of the mechanism of muscle function loss in dystrophin-deficient C. elegans, leading to knowledge translatable to human muscular dystrophy.

U2 - 10.1242/dmm.036137

DO - 10.1242/dmm.036137

M3 - Journal article

VL - 11

JO - Disease Models & Mechanisms

JF - Disease Models & Mechanisms

IS - 11

M1 - 36137

ER -