Mechanisms of skeletal muscle wasting in a mouse model for myotonic dystrophy type 1

Human Molecular Genetics
Ginny R MorrissThomas A Cooper

Abstract

Myotonic dystrophy type 1 (DM1) is a multi-systemic disease resulting in severe muscle weakening and wasting. DM1 is caused by expansion of CTG repeats in the 3' untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. We have developed an inducible, skeletal muscle-specific mouse model of DM1 (CUG960) that expresses 960 CUG repeat-expressing animals (CUG960) in the context of human DMPK exons 11-15. CUG960 RNA-expressing mice induced at postnatal day 1, as well as adult-onset animals, show clear, measurable muscle wasting accompanied by severe histological defects including central myonuclei, reduced fiber cross-sectional area, increased percentage of oxidative myofibers, the presence of nuclear RNA foci that colocalize with Mbnl1 protein, and increased Celf1 protein in severely affected muscles. Importantly, muscle loss, histological abnormalities and RNA foci are reversible, demonstrating recovery upon removal of toxic RNA. RNA-seq and protein array analysis indicate that the balance between anabolic and catabolic pathways that normally regulate muscle mass may be disrupted by deregulation of platelet derived growth factor receptor β signaling and the PI3K/AKT pathways, along with prolonged activation of A...Continue Reading

References

Mar 1, 1995·The Journal of Cell Biology·K L TanejaR H Singer
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·B M DavisD E Housman
Oct 9, 2001·Human Molecular Genetics·A MankodiC A Thornton
Dec 19, 2003·Annals of Neurology·Ami MankodiCharles A Thornton
Jan 15, 2004·The Journal of Biological Chemistry·Nikolai A TimchenkoLubov T Timchenko
Jun 1, 2004·Nature Medicine·Eric P Hoffman, Gustavo A Nader
May 4, 2005·Molecular Cell·Russell G JonesCraig B Thompson
Nov 10, 2005·Molecular and Cellular Neurosciences·Olga N PonomarevaMendell Rimer
May 24, 2006·Human Molecular Genetics·Xiaoyan LinCharles A Thornton
Jul 26, 2006·Proceedings of the National Academy of Sciences of the United States of America·Rahul N KanadiaMaurice S Swanson
Aug 1, 2006·Nature Genetics·Mani S MahadevanLawrence H Phillips
Apr 7, 2007·PLoS Genetics·Mário Gomes-PereiraGeneviève Gourdon
Feb 5, 2008·Molecular Cell·Irina A VlasovaPaul R Bohjanen
Feb 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·James P OrengoThomas A Cooper
Sep 18, 2008·International Journal of Obesity : Journal of the International Association for the Study of Obesity·D G Hardie
Nov 1, 2008·Nature Protocols·Brett SpurrierSatoshi Nishizuka
Nov 4, 2008·Nature·Eric T WangChristopher B Burge
Dec 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Auinash KalsotraThomas A Cooper
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Mar 18, 2009·Bioinformatics·Cole TrapnellSteven L Salzberg
Mar 24, 2009·Nature Methods·Enrico K SchmidtPhilippe Pierre
Jul 10, 2009·International Journal of Cancer. Journal International Du Cancer·Marcin WysoczynskiMariusz Z Ratajczak
May 1, 2010·Cell Death and Differentiation·E LoroL Vergani
Jul 7, 2010·Human Molecular Genetics·Amanda J WardThomas A Cooper
Aug 28, 2010·The International Journal of Biochemistry & Cell Biology·Pascale BeffyMarcella Simili
Nov 9, 2010·Nature Methods·Yarden KatzChristopher B Burge
Jun 21, 2011·Nature Structural & Molecular Biology·Frédérique RauNicolas Charlet-Berguerand
Jul 5, 2011·Trends in Molecular Medicine·Mário Gomes-PereiraGeneviève Gourdon
Aug 9, 2011·Human Molecular Genetics·Géraldine SicotMário Gomes-Pereira
Sep 6, 2011·Nature Cell Biology·Maria M Mihaylova, Reuben J Shaw

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Citations

Dec 19, 2018·Human Molecular Genetics·Eric T WangChristopher Burge
Apr 13, 2019·Proceedings of the National Academy of Sciences of the United States of America·JuYeon LeeSteven C Zimmerman
Jun 7, 2020·Human Molecular Genetics·Tara E Crawford ParksAymeric Ravel-Chapuis
Dec 4, 2020·Biological Reviews of the Cambridge Philosophical Society·Lauren L OzimskiRuben Artero
Mar 9, 2021·Journal of Neuromuscular Diseases·Valentina GrandeAndreas Roos
Apr 18, 2021·Human Molecular Genetics·Ramesh S YadavaMani S Mahadevan
May 16, 2021·Molecular & Cellular Proteomics : MCP·Jill S NapieralaMarek Napierala
Dec 20, 2019·Molecular Therapy. Nucleic Acids·Maria Sabater-ArcisRuben Artero

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