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Absence of p.R50X Pygm read-through in McArdle disease cellular models

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Harvard

Tarrasó, G, Real-Martinez, A, Parés, M, Romero-Cortadellas, L, Puigros, L, Moya, L, de Luna, N, Brull, A, Martín, MA, Arenas, J, Lucia, A, Andreu, AL, Barquinero, J, Vissing, J, Krag, TO & Pinós, T 2020, 'Absence of p.R50X Pygm read-through in McArdle disease cellular models' Disease models & mechanisms, vol. 13, no. 1, pp. dmm043281. . https://doi.org/10.1242/dmm.043281

APA

Tarrasó, G., Real-Martinez, A., Parés, M., Romero-Cortadellas, L., Puigros, L., Moya, L., ... Pinós, T. (2020). Absence of p.R50X Pygm read-through in McArdle disease cellular models. Disease models & mechanisms, 13(1), dmm043281. https://doi.org/10.1242/dmm.043281

CBE

Tarrasó G, Real-Martinez A, Parés M, Romero-Cortadellas L, Puigros L, Moya L, de Luna N, Brull A, Martín MA, Arenas J, Lucia A, Andreu AL, Barquinero J, Vissing J, Krag TO, Pinós T. 2020. Absence of p.R50X Pygm read-through in McArdle disease cellular models. Disease models & mechanisms. 13(1):dmm043281. . https://doi.org/10.1242/dmm.043281

MLA

Vancouver

Tarrasó G, Real-Martinez A, Parés M, Romero-Cortadellas L, Puigros L, Moya L et al. Absence of p.R50X Pygm read-through in McArdle disease cellular models. Disease models & mechanisms. 2020 Jan 13;13(1):dmm043281. . https://doi.org/10.1242/dmm.043281

Author

Tarrasó, Guillermo ; Real-Martinez, Alberto ; Parés, Marta ; Romero-Cortadellas, Lídia ; Puigros, Laura ; Moya, Laura ; de Luna, Noemí ; Brull, Astrid ; Martín, Miguel Angel ; Arenas, Joaquin ; Lucia, Alejandro ; Andreu, Antoni L ; Barquinero, Jordi ; Vissing, John ; Krag, Thomas O ; Pinós, Tomàs. / Absence of p.R50X Pygm read-through in McArdle disease cellular models. In: Disease models & mechanisms. 2020 ; Vol. 13, No. 1. pp. dmm043281. .

Bibtex

@article{fa3fd175e3f148b0b3fb147e7a6c46f6,
title = "Absence of p.R50X Pygm read-through in McArdle disease cellular models",
abstract = "McArdle disease is an autosomal recessive disorder caused by the absence of muscle glycogen phosphorylase, which leads to blocked muscle glycogen breakdown. We used three different cellular models to evaluate the efficiency of different read-through agents (including amlexanox, Ataluren, RTC13 and G418) in McArdle disease. The first model consisted of HeLa cells transfected with two different GFP-PYGM constructs presenting the Pygm p.R50X mutation (GFP-PYGM p.R50X and PYGM Ex1-GFP p.R50X). The second cellular model was based on the creation of HEK293T cell lines stably expressing the PYGM Ex1-GFP p.R50X construct. As these plasmids encode murine Pygm cDNA without any intron sequence, their transfection in cells would allow for analysis of the efficacy of read-through agents with no concomitant nonsense-mediated decay interference. The third model consisted of skeletal muscle cultures derived from the McArdle mouse model (knock-in for the p.R50X mutation in the Pygm gene). We found no evidence of read-through at detectable levels in any of the models evaluated. We performed a literature search and compared the premature termination codon context sequences with reported positive and negative read-through induction, identifying a potential role for nucleotide positions -9, -8, -3, -2, +13 and +14 (the first nucleotide of the stop codon is assigned as +1). The Pygm p.R50X mutation presents TGA as a stop codon, G nucleotides at positions -1 and -9, and a C nucleotide at -3, which potentially generate a good context for read-through induction, counteracted by the presence of C at -2 and its absence at +4.",
author = "Guillermo Tarras{\'o} and Alberto Real-Martinez and Marta Par{\'e}s and L{\'i}dia Romero-Cortadellas and Laura Puigros and Laura Moya and {de Luna}, Noem{\'i} and Astrid Brull and Mart{\'i}n, {Miguel Angel} and Joaquin Arenas and Alejandro Lucia and Andreu, {Antoni L} and Jordi Barquinero and John Vissing and Krag, {Thomas O} and Tom{\`a}s Pin{\'o}s",
note = "{\circledC} 2020. Published by The Company of Biologists Ltd.",
year = "2020",
month = "1",
day = "13",
doi = "10.1242/dmm.043281",
language = "English",
volume = "13",
pages = "dmm043281.",
journal = "DMM Disease Models and Mechanisms",
issn = "1754-8403",
publisher = "company of biologists",
number = "1",

}

RIS

TY - JOUR

T1 - Absence of p.R50X Pygm read-through in McArdle disease cellular models

AU - Tarrasó, Guillermo

AU - Real-Martinez, Alberto

AU - Parés, Marta

AU - Romero-Cortadellas, Lídia

AU - Puigros, Laura

AU - Moya, Laura

AU - de Luna, Noemí

AU - Brull, Astrid

AU - Martín, Miguel Angel

AU - Arenas, Joaquin

AU - Lucia, Alejandro

AU - Andreu, Antoni L

AU - Barquinero, Jordi

AU - Vissing, John

AU - Krag, Thomas O

AU - Pinós, Tomàs

N1 - © 2020. Published by The Company of Biologists Ltd.

PY - 2020/1/13

Y1 - 2020/1/13

N2 - McArdle disease is an autosomal recessive disorder caused by the absence of muscle glycogen phosphorylase, which leads to blocked muscle glycogen breakdown. We used three different cellular models to evaluate the efficiency of different read-through agents (including amlexanox, Ataluren, RTC13 and G418) in McArdle disease. The first model consisted of HeLa cells transfected with two different GFP-PYGM constructs presenting the Pygm p.R50X mutation (GFP-PYGM p.R50X and PYGM Ex1-GFP p.R50X). The second cellular model was based on the creation of HEK293T cell lines stably expressing the PYGM Ex1-GFP p.R50X construct. As these plasmids encode murine Pygm cDNA without any intron sequence, their transfection in cells would allow for analysis of the efficacy of read-through agents with no concomitant nonsense-mediated decay interference. The third model consisted of skeletal muscle cultures derived from the McArdle mouse model (knock-in for the p.R50X mutation in the Pygm gene). We found no evidence of read-through at detectable levels in any of the models evaluated. We performed a literature search and compared the premature termination codon context sequences with reported positive and negative read-through induction, identifying a potential role for nucleotide positions -9, -8, -3, -2, +13 and +14 (the first nucleotide of the stop codon is assigned as +1). The Pygm p.R50X mutation presents TGA as a stop codon, G nucleotides at positions -1 and -9, and a C nucleotide at -3, which potentially generate a good context for read-through induction, counteracted by the presence of C at -2 and its absence at +4.

AB - McArdle disease is an autosomal recessive disorder caused by the absence of muscle glycogen phosphorylase, which leads to blocked muscle glycogen breakdown. We used three different cellular models to evaluate the efficiency of different read-through agents (including amlexanox, Ataluren, RTC13 and G418) in McArdle disease. The first model consisted of HeLa cells transfected with two different GFP-PYGM constructs presenting the Pygm p.R50X mutation (GFP-PYGM p.R50X and PYGM Ex1-GFP p.R50X). The second cellular model was based on the creation of HEK293T cell lines stably expressing the PYGM Ex1-GFP p.R50X construct. As these plasmids encode murine Pygm cDNA without any intron sequence, their transfection in cells would allow for analysis of the efficacy of read-through agents with no concomitant nonsense-mediated decay interference. The third model consisted of skeletal muscle cultures derived from the McArdle mouse model (knock-in for the p.R50X mutation in the Pygm gene). We found no evidence of read-through at detectable levels in any of the models evaluated. We performed a literature search and compared the premature termination codon context sequences with reported positive and negative read-through induction, identifying a potential role for nucleotide positions -9, -8, -3, -2, +13 and +14 (the first nucleotide of the stop codon is assigned as +1). The Pygm p.R50X mutation presents TGA as a stop codon, G nucleotides at positions -1 and -9, and a C nucleotide at -3, which potentially generate a good context for read-through induction, counteracted by the presence of C at -2 and its absence at +4.

U2 - 10.1242/dmm.043281

DO - 10.1242/dmm.043281

M3 - Journal article

VL - 13

SP - dmm043281.

JO - DMM Disease Models and Mechanisms

JF - DMM Disease Models and Mechanisms

SN - 1754-8403

IS - 1

ER -

ID: 59289416