Loss of sparc in mouse skeletal muscle causes myofiber atrophy

Nakamura, Katsuyuki; Nakano, Shinichi; Miyoshi, Takahiro; Yamanouchi, Keitaro; Nishihara, Masugi

doi:10.1002/mus.23822

Cited by 37 publications

(46 citation statements)

References 43 publications

(76 reference statements)

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“…Histological analyses were performed using a previously published method30. Briefly, frozen sections (7–8-μm thick) of TA muscles were prepared transversely, and paraffin-embedded sections of the heart and diaphragm were subjected to histological analyses.…”

Section: Methodsmentioning

confidence: 99%

Generation of muscular dystrophy model rats with a CRISPR/Cas system

Nakamura

Fujii

Tsuboi

et al. 2014

Sci Rep

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135

144

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Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disorder caused by mutations in the Dmd gene encoding Dystrophin12. DMD model animals, such as mdx mice and canine X-linked muscular dystrophy dogs, have been widely utilized in the development of a treatment for DMD3. Here, we demonstrate the generation of Dmd-mutated rats using a clustered interspaced short palindromic repeats (CRISPR)/Cas system, an RNA-based genome engineering technique that is also adaptive to rats. We simultaneously targeted two exons in the rat Dmd gene, which resulted in the absence of Dystrophin expression in the F0 generation. Dmd-mutated rats exhibited a decline in muscle strength, and the emergence of degenerative/regenerative phenotypes in the skeletal muscle, heart, and diaphragm. These mutations were heritable by the next generation, and F1 male rats exhibited similar phenotypes in their skeletal muscles. These model rats should prove to be useful for developing therapeutic methods to treat DMD.

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Section: Methodsmentioning

confidence: 99%

Generation of muscular dystrophy model rats with a CRISPR/Cas system

Nakamura

Fujii

Tsuboi

et al. 2014

Sci Rep

Self Cite

135

144

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“…Each of these genes was elevated in BCATm KO mice (Supplementary Tables S1-S3). Another link to these genes and TGF-beta is decreased expression of Sparc (osteonectin) gene expression in BCATm KO mice (Supplementary Tables S1-S3), which is associated with myofibrillar atrophy (60). A gene encoding another protein, osteopontin (Spp1), is induced following muscle injury and is thought to be an important factor in the degenerative and regenerative events associated with muscle injury (for review see Ref.…”

Section: Upstream Pathway Analysismentioning

confidence: 99%

Global deletion ofBCATmincreases expression of skeletal muscle genes associated with protein turnover

Lynch

Kimball

et al. 2015

Physiological Genomics

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Lynch CJ, Kimball SR, Xu Y, Salzberg AC, Kawasawa YI. Global deletion of BCATm increases expression of skeletal muscle genes associated with protein turnover. Physiol Genomics 47: 569-580, 2015. First published September 8, 2015 doi:10.1152/physiolgenomics.00055.2015.-Consumption of a protein-containing meal by a fasted animal promotes protein accretion in skeletal muscle, in part through leucine stimulation of protein synthesis and indirectly through repression of protein degradation mediated by its metabolite, ␣-ketoisocaproate. Mice lacking the mitochondrial branched-chain aminotransferase (BCATm/Bcat2), which interconverts leucine and ␣-ketoisocaproate, exhibit elevated protein turnover. Here, the transcriptomes of gastrocnemius muscle from BCATm knockout (KO) and wildtype mice were compared by next-generation RNA sequencing (RNA-Seq) to identify potential adaptations associated with their persistently altered nutrient signaling. Statistically significant changes in the abundance of 1,486/ϳ39,010 genes were identified. Bioinformatics analysis of the RNA-Seq data indicated that pathways involved in protein synthesis [eukaryotic initiation factor (eIF)-2, mammalian target of rapamycin, eIF4, and p70S6K pathways including 40S and 60S ribosomal proteins], protein breakdown (e.g., ubiquitin mediated), and muscle degeneration (apoptosis, atrophy, myopathy, and cell death) were upregulated. Also in agreement with our previous observations, the abundance of mRNAs associated with reduced body size, glycemia, plasma insulin, and lipid signaling pathways was altered in BCATm KO mice. Consistently, genes encoding anaerobic and/or oxidative metabolism of carbohydrate, fatty acids, and branched chain amino acids were modestly but systematically reduced. Although there was no indication that muscle fiber type was different between KO and wild-type mice, a difference in the abundance of mRNAs associated with a muscular dystrophy phenotype was observed, consistent with the published exercise intolerance of these mice. The results suggest transcriptional adaptations occur in BCATm KO mice that along with altered nutrient signaling may contribute to their previously reported protein turnover, metabolic and exercise phenotypes.

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“…Briefly, frozen sections (7-8-mm thick) of gastrocnemius muscles were sectioned transversely, and paraffin-embedded sections of the muscle were subjected to histological analyses. Fibrosis staining was performed according to the published method [37] with slight modification. Briefly, paraffin sections of gastrocnemius were incubated with 5% BSA for 30 min, with1:100 primary antibodies against dystrophin (Abcam, UK) at 4°C overnight and then with1:100 FITC-conjugated secondary antibody (Cell Signaling Technology, USA) for 1 h at room temperature.…”

Section: Immunoblottingmentioning

confidence: 99%

Long Noncoding RNA Lnc-SEMT Modulates IGF2 Expression by Sponging miR-125b to Promote Sheep Muscle Development and Growth

Wei¹,

Wu²,

Wang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Long noncoding RNAs (lncRNAs) are RNA transcripts that are more than 200 nt long but have little protein-coding potential. Within the last few years, thousands of lncRNAs have been identified and their functions in biological processes have begun to be understood. Although many studies havebegun to examine the functions of many noncoding RNAs, very little is known about the functions of long noncoding (lncRNA) function of livestock production and molecular mechanisms of their functions are still lackingrelated to livestock production. Methods: Expression of sheep enhanced muscularityTranscript lncRNA (lnc-SEMT) and miR-125b were examined in sheep using quantitative reverse-transcription polymerase chain reaction. Expression of Myod (myogenic determination factor), Myog (myoglobin) and Insulin-like growth factor 2 (IGF2)were examined by Western Blot.Luciferase reporter assays were performedto confirm the relationship between lnc-SEMT and miR-125b. Results: Here, we identified a novel lnc-SEMT that promote sheep myoblast differentiation in vitro and enhanced sheep muscularity in vivo. Functional analyses showed that lnc-SEMT accelerates sheep myoblast differentiation in vitro. lnc-SEMT transgenic sheep exhibit a muscle hypertrophy phenotype characterized by increased body weight, and increased the number of muscle fibers indicating that lnc-SEMT play an important role in the regulation of skeletal muscle differentiation in vivo. Our results show that lnc-SEMT acts as a molecular sponge by antagonizing miR-125b to control IGF2 protein labundance in vitro and in vivo. Conclusion: In brief, lnc-SEMT is the first example of a lncRNA could be a useful candidate for improving biological growth traits such as skeletal muscle production in sheep.

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Loss of sparc in mouse skeletal muscle causes myofiber atrophy

Abstract: The loss of SPARC not only upregulates atrogin1 expression but also enhances TGFβ signaling, which may in turn cause muscle atrophy.

Cited by 37 publications

References 43 publications

Generation of muscular dystrophy model rats with a CRISPR/Cas system

Generation of muscular dystrophy model rats with a CRISPR/Cas system

Global deletion ofBCATmincreases expression of skeletal muscle genes associated with protein turnover

Long Noncoding RNA Lnc-SEMT Modulates IGF2 Expression by Sponging miR-125b to Promote Sheep Muscle Development and Growth

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