Msi2 enhances muscle dysfunction in a myotonic dystrophy type 1 mouse model

Sabater-Arcis, Maria; Moreno, Nerea; Sevilla, Teresa; Perez Alonso, Manuel; Bargiela, Ariadna; Artero, Ruben

doi:10.1016/j.bj.2023.100667

Cited by 3 publications

(1 citation statement)

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“…In addition to their roles as splicing factors, these proteins have a myriad of functions in RNA processing and localization [ 11 ]. There is also experimental evidence for other mechanisms involving transcription factors, signaling such as the glycogen synthase kinase 3-beta (GSK-3β), AKT, AMPK, PKC, Tweak/Fn14, PI3K/AKT pathways, other RNA binding proteins (e.g., hnRNPA1 and MSI2), circular RNA generation, microRNAs, mitochondrial dysfunction, increased cellular senescence, and most recently, calcium channel dysfunction in conjunction with chloride channel dysfunction [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. However, the strongest evidence is for the loss of function of MBNL proteins due to binding to the mutant RNA and their sequestration in the RNA foci [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Studying the Effect of MBNL1 and MBNL2 Loss in Skeletal Muscle Regeneration

Yadava,

Mandal,

Mahadevan

2024

IJMS

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Loss of function of members of the muscleblind-like (MBNL) family of RNA binding proteins has been shown to play a key role in the spliceopathy of RNA toxicity in myotonic dystrophy type 1 (DM1), the most common muscular dystrophy affecting adults and children. MBNL1 and MBNL2 are the most abundantly expressed members in skeletal muscle. A key aspect of DM1 is poor muscle regeneration and repair, leading to dystrophy. We used a BaCl2-induced damage model of muscle injury to study regeneration and effects on skeletal muscle satellite cells (MuSCs) in Mbnl1∆E3/∆E3 and Mbnl2∆E2/∆E2 knockout mice. Similar experiments have previously shown deleterious effects on these parameters in mouse models of RNA toxicity. Muscle regeneration in Mbnl1 and Mbnl2 knockout mice progressed normally with no obvious deleterious effects on MuSC numbers or increased expression of markers of fibrosis. Skeletal muscles in Mbnl1∆E3/∆E3/ Mbnl2∆E2/+ mice showed increased histopathology but no deleterious reductions in MuSC numbers and only a slight increase in collagen deposition. These results suggest that factors beyond the loss of MBNL1/MBNL2 and the associated spliceopathy are likely to play a key role in the defects in skeletal muscle regeneration and deleterious effects on MuSCs that are seen in mouse models of RNA toxicity due to expanded CUG repeats.

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