Studying the Effect of MBNL1 and MBNL2 Loss in Skeletal Muscle Regeneration
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 abundantl...
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MDPI AG
2024-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/5/2687 |
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| author | Ramesh S. Yadava Mahua Mandal Mani S. Mahadevan |
| author_facet | Ramesh S. Yadava Mahua Mandal Mani S. Mahadevan |
| author_sort | Ramesh S. Yadava |
| collection | DOAJ |
| description | 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 BaCl<sub>2</sub>-induced damage model of muscle injury to study regeneration and effects on skeletal muscle satellite cells (MuSCs) in <i>Mbnl1<sup>∆E3</sup></i><sup>/<i>∆E3</i></sup> and <i>Mbnl2<sup>∆E2</sup></i><sup>/<i>∆E2</i></sup> knockout mice. Similar experiments have previously shown deleterious effects on these parameters in mouse models of RNA toxicity. Muscle regeneration in <i>Mbnl1</i> and <i>Mbnl2</i> knockout mice progressed normally with no obvious deleterious effects on MuSC numbers or increased expression of markers of fibrosis. Skeletal muscles in <i>Mbnl1<sup>∆E3</sup></i><sup>/<i>∆E3</i></sup><i>/ Mbnl2<sup>∆E2</sup></i><sup>/+</sup> 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. |
| first_indexed | 2024-04-25T00:29:05Z |
| format | Article |
| id | doaj.art-82d5e651b5664e9fa4e611843a66a492 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-25T00:29:05Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-82d5e651b5664e9fa4e611843a66a4922024-03-12T16:45:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01255268710.3390/ijms25052687Studying the Effect of MBNL1 and MBNL2 Loss in Skeletal Muscle RegenerationRamesh S. Yadava0Mahua Mandal1Mani S. Mahadevan2Department of Pathology, University of Virginia, Charlottesville, VA 22908, USADepartment of Pathology, University of Virginia, Charlottesville, VA 22908, USADepartment of Pathology, University of Virginia, Charlottesville, VA 22908, USALoss 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 BaCl<sub>2</sub>-induced damage model of muscle injury to study regeneration and effects on skeletal muscle satellite cells (MuSCs) in <i>Mbnl1<sup>∆E3</sup></i><sup>/<i>∆E3</i></sup> and <i>Mbnl2<sup>∆E2</sup></i><sup>/<i>∆E2</i></sup> knockout mice. Similar experiments have previously shown deleterious effects on these parameters in mouse models of RNA toxicity. Muscle regeneration in <i>Mbnl1</i> and <i>Mbnl2</i> knockout mice progressed normally with no obvious deleterious effects on MuSC numbers or increased expression of markers of fibrosis. Skeletal muscles in <i>Mbnl1<sup>∆E3</sup></i><sup>/<i>∆E3</i></sup><i>/ Mbnl2<sup>∆E2</sup></i><sup>/+</sup> 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.https://www.mdpi.com/1422-0067/25/5/2687muscle regenerationmyotonic dystrophyRNA toxicitysatellite cellsmuscleblindRNA binding proteins |
| spellingShingle | Ramesh S. Yadava Mahua Mandal Mani S. Mahadevan Studying the Effect of MBNL1 and MBNL2 Loss in Skeletal Muscle Regeneration International Journal of Molecular Sciences muscle regeneration myotonic dystrophy RNA toxicity satellite cells muscleblind RNA binding proteins |
| title | Studying the Effect of MBNL1 and MBNL2 Loss in Skeletal Muscle Regeneration |
| title_full | Studying the Effect of MBNL1 and MBNL2 Loss in Skeletal Muscle Regeneration |
| title_fullStr | Studying the Effect of MBNL1 and MBNL2 Loss in Skeletal Muscle Regeneration |
| title_full_unstemmed | Studying the Effect of MBNL1 and MBNL2 Loss in Skeletal Muscle Regeneration |
| title_short | Studying the Effect of MBNL1 and MBNL2 Loss in Skeletal Muscle Regeneration |
| title_sort | studying the effect of mbnl1 and mbnl2 loss in skeletal muscle regeneration |
| topic | muscle regeneration myotonic dystrophy RNA toxicity satellite cells muscleblind RNA binding proteins |
| url | https://www.mdpi.com/1422-0067/25/5/2687 |
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