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Life-long reduction in myomiR expression does not adversely affect skeletal muscle morphology
Department of Physiology, College of Medicine, University of Kentucky, Kentucky, USA; Center for Muscle Biology University of Kentucky, Lexington, Kentucky, USA; Department of Morphology, São Paulo State University, Institute of Biosciences, Botucatu, Brazil.
Department of Physiology, College of Medicine, University of Kentucky, Kentucky, USA; Center for Muscle Biology University of Kentucky, Lexington, Kentucky, USA.
Örebro University, School of Health Sciences.ORCID iD: 0000-0002-5322-4150
Department of Rehabilitation Sciences, College of Health Sciences, Kentucky, USA; Center for Muscle Biology University of Kentucky, Lexington, Kentucky, USA.
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, article id 5483Article in journal (Refereed) Published
Abstract [en]

We generated an inducible, skeletal muscle-specific Dicer knockout mouse to deplete microRNAs in adult skeletal muscle. Following tamoxifen treatment, Dicer mRNA expression was significantly decreased by 87%. Wild-type (WT) and Dicer knockout (KO) mice were subjected to either synergist ablation or hind limb suspension for two weeks. There was no difference in muscle weight with hypertrophy or atrophy between WT and KO groups; however, even with the significant loss of Dicer expression, myomiR (miR-1, -133a and -206) expression was only reduced by 38% on average. We next aged WT and KO mice for ~22 months following Dicer inactivation to determine if myomiR expression would be further reduced over a prolonged timeframe and assess the effects of myomiR depletion on skeletal muscle phenotype. Skeletal muscle Dicer mRNA expression remained significantly decreased by 80% in old KO mice and sequencing of cloned Dicer mRNA revealed the complete absence of the floxed exons in KO skeletal muscle. Despite a further reduction of myomiR expression to ~50% of WT, no change was observed in muscle morphology between WT and KO groups. These results indicate the life-long reduction in myomiR levels did not adversely affect skeletal muscle phenotype and suggest the possibility that microRNA expression is uniquely regulated in skeletal muscle.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019. Vol. 9, no 1, article id 5483
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Physiology
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URN: urn:nbn:se:oru:diva-73536DOI: 10.1038/s41598-019-41476-8ISI: 000462990000025PubMedID: 30940834Scopus ID: 2-s2.0-85063882282OAI: oai:DiVA.org:oru-73536DiVA, id: diva2:1303028
Note

Funding Agencies:

Sao Paulo Research Foundation, Brazil (FAPESP)  2014/24327-1  2015/19193-9 

NIH  AR061939  AR071753 

Available from: 2019-04-08 Created: 2019-04-08 Last updated: 2019-06-19Bibliographically approved

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Chaillou, Thomas

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