Expression profiling reveals altered satellite cell numbers and glycolytic enzyme transcription in nemaline myopathy muscle

Despina Sanoudou, Judith N. Haslett, Alvin T. Kho, Shaoqiang Guo, Hanna T. Gazda, Steven A. Greenberg, Hart G W Lidov, Isaac S. Kohane, Louis M. Kunkel, Alan H. Beggs

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58 Citations (Scopus)

Abstract

The nemaline myopathies (NMs) are a clinically and genetically heterogeneous group of disorders characterized by nemaline rods and skeletal muscle weakness. Mutations in five sarcomeric thin filament genes have been identified. However, the molecular consequences of these mutations are unknown. Using Affymetrix oligonucleotide microarrays, we have analyzed the expression patterns of >21,000 genes and expressed sequence tags in skeletal muscles of 12 NM patients and 21 controls. Multiple complementary approaches were used for data analysis, including geometric fold analysis, two-tailed unequal variance test, hierarchical clustering, relevance network, and nearest-neighbor analysis. We report the identification of high satellite cell populations in NM and the significant down-regulation of transcripts for key enzymes of glucose and glycogen metabolism as well as a possible regulator of fatty acid metabolism, UCP3. Interestingly, transcript level changes of multiple genes suggest possible changes in Ca2+ homeostasis. The increased expression of multiple structural proteins was consistent with increased fibrosis. This comprehensive study of downstream molecular consequences of NM gene mutations provides insights in the cellular events leading to the NM phenotype.

Original languageEnglish
Pages (from-to)4666-4671
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number8
DOIs
Publication statusPublished - 15 Apr 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Sanoudou, D., Haslett, J. N., Kho, A. T., Guo, S., Gazda, H. T., Greenberg, S. A., Lidov, H. G. W., Kohane, I. S., Kunkel, L. M., & Beggs, A. H. (2003). Expression profiling reveals altered satellite cell numbers and glycolytic enzyme transcription in nemaline myopathy muscle. Proceedings of the National Academy of Sciences of the United States of America, 100(8), 4666-4671. https://doi.org/10.1073/pnas.0330960100