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Genome-wide expression analysis comparing hypertrophic changes in normal and dysferlinopathy mice
Yun-Sil Lee1, C Conover Talbot2, Se-Jin Lee1
1Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, PCTB 803, Baltimore, MD 21205, USA.
Abstract:
Because myostatin normally limits skeletal muscle growth, there are extensive efforts to develop myostatin inhibitors for clinical use. One potential concern is that in muscle degenerative diseases, inducing hypertrophy may increase stress on dystrophic fibers. Our study shows that blocking this pathway in dysferlin deficient mice results in early improvement in histopathology but ultimately accelerates muscle degeneration. Hence, benefits of this approach should be weighed against these potential detrimental effects. Here, we present detailed experimental methods and analysis for the gene expression profiling described in our recently published study in Human Molecular Genetics (Lee et al., 2015). Our data sets have been deposited in the Gene Expression Omnibus (GEO) database (GSE62945) and are available at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62945. Our data provide a resource for exploring molecular mechanisms that are related to hypertrophy-induced, accelerated muscular degeneration in dysferlinopathy.
Insights
Blocking myostatin to promote muscle growth in dysferlinopathy mice initially improves muscle but accelerates degeneration. These findings highlight potential risks of myostatin inhibitors in muscular dystrophy.
Area of Science:
- Biochemistry
- Genetics
- Molecular Biology
Background:
- Myostatin is a key regulator of skeletal muscle mass.
- Myostatin inhibitors are being developed for muscle-wasting conditions.
- Inducing muscle hypertrophy in degenerative diseases may pose risks.
Purpose of the Study:
- To investigate the effects of myostatin inhibition on dysferlin-deficient mice.
- To analyze gene expression changes associated with hypertrophy-induced degeneration.
- To provide a data resource for understanding dysferlinopathy.
Main Methods:
- Gene expression profiling using microarrays.
- Histopathological analysis of muscle tissue.
- Bioinformatic analysis of gene expression data.
Main Results:
- Myostatin inhibition led to early histopathological improvements in dysferlin-deficient mice.
- However, myostatin inhibition ultimately accelerated muscle degeneration.
- Gene expression data revealed molecular mechanisms underlying accelerated degeneration.
Conclusions:
- Myostatin inhibition may have detrimental effects in dysferlinopathy.
- The benefits of myostatin inhibitors in muscular dystrophy require careful consideration.
- The study provides valuable data for further research into muscular degeneration.
