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The influence of muscle type and dystrophin deficiency on murine expression profiles

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Abstract

The phenotypic differences among Duchenne muscular dystrophy patients, mdx mice, and mdx5cv mice suggest that despite the common etiology of dystrophin deficiency, secondary mechanisms have a substantial influence on phenotypic severity. The differential response of various skeletal muscles to dystrophin deficiency supports this hypothesis. To explore these differences, gene expression profiles were generated from duplicate RNA targets extracted from six different skeletal muscles (diaphragm, soleus, gastrocnemius, quadriceps, tibialis anterior, and extensor digitorum longus) from wild-type, mdx, and mdx5cv mice, resulting in 36 data sets for 18 muscle samples. The data sets were compared in three different ways: (1) among wild-type samples only, (2) among all 36 data sets, and (3) between strains for each muscle type. The molecular profiles of soleus and diaphragm separate significantly from the other four muscle types and from each other. Fiber-type proportions can explain some of these differences. These variations in wild-type gene expression profiles may also reflect biomechanical differences known to exist among skeletal muscles. Further exploration of the genes that most distinguish these muscles may help explain the origins of the biomechanical differences and the reasons why some muscles are more resistant than others to dystrophin deficiency.

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Acknowledgments

The authors thank Marielle Thorne for her assistance. This work was supported by NIH grants P01 NS40828-01A1 (ISK, AHB, LMK), R01 AR44349 (AHB), U01 HL066582-01 (ISK), and K08 NS048180 (PBK), the Muscular Dystrophy Association (PBK, AHB, LMK), the Bernard F. and Alva B. Gimbel Foundation (LMK), the Joshua Frase Foundation (AHB, LMK), and the William Randolph Hearst Foundation (PBK).

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Authors and Affiliations

  1. Division of Genetics and Genomics Program, Children’s Hospital Boston and Harvard Medical School, Boston, Massachusetts, 02115, USA

    Judith N. Haslett, Peter B. Kang, Mei Han, Despina Sanoudou, Jay M. Volinski, Alan H. Beggs & Louis M. Kunkel

  2. Department of Neurology, Children’s Hospital Boston and Harvard Medical School, Boston, Massachusetts, 02115, USA

    Peter B. Kang

  3. Informatics Program, Children’s Hospital Boston and Harvard Medical School, Boston, Massachusetts, 02115, USA

    Alvin T. Kho & Isaac S. Kohane

  4. Division of Endocrinology, Children’s Hospital Boston and Harvard Medical School, Boston, Massachusetts, 02115, USA

    Isaac S. Kohane

  5. Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, Maryland, 20815, USA

    Louis M. Kunkel

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  1. Judith N. Haslett
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  2. Peter B. Kang
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  3. Mei Han
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  4. Alvin T. Kho
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  6. Jay M. Volinski
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  9. Louis M. Kunkel
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Correspondence to Louis M. Kunkel.

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Judith N. Haslett, Peter B. Kang These authors contributed equally to this work.

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Haslett, J.N., Kang, P.B., Han, M. et al. The influence of muscle type and dystrophin deficiency on murine expression profiles. Mamm Genome 16, 739–748 (2005). https://doi.org/10.1007/s00335-005-0053-8

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  • DOI: https://doi.org/10.1007/s00335-005-0053-8

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