Skip Navigation



Human Molecular Genetics Advance Access published online on June 9, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh174
© 2004 by Oxford University Press
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
13/15/1669    most recent
ddh174v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Yue, Y.
Right arrow Articles by Duan, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yue, Y.
Right arrow Articles by Duan, D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Article

Full-length dystrophin expression in half of the heart cells ameliorates {beta}-isoproterenol-induced cardiomyopathy in mdx mice

Yongping Yue 1, Jeffrey W. Skimming 2, Mingju Liu 1, Tammy Strawn 2, Dongsheng Duan 3*

1 Department of Molecular Microbiology and Immunology, The University of Missouri, School of Medicine
2 Department of Child Health and Department of Medical Pharmacology and Physiology, The University of Missouri, School of Medicine
3 Department of Molecular Microbiology and Immunology, The University of Missouri, School of Medicine, One Hospital Dr., Room M610G, MSB, Columbia, MO 65212

* To whom correspondence should be addressed. E-mail: duand{at}missouri.edu.


  Abstract

Gene therapy holds great promise for curing Duchenne muscular dystrophy (DMD), the most common fatal inherited childhood muscle disease. Success of DMD gene therapy depends upon functional improvement in both skeletal and cardiac muscle. Numerous gene transfer studies have been performed to correct skeletal muscle pathology, yet little is known about cardiomyopathy gene therapy. Since complete transduction of the entire heart is an impractical goal, it becomes critical to determine the minimal level of correction needed for successful DMD cardiomyopathy gene therapy. To address this question, we generated heterozygous mice that persistently expressed the full-length dystrophin gene in 50% of the cardiomyocytes of mdx mice, a model for DMD. We asked whether dystrophin expression in half of the heart cells was sufficient to prevent stress-induced cardiomyopathy. Mdx mouse heart function is normal in the absence of external stress. To determine the therapeutic effect, we challenged three-month-old mice with {beta}-isoproterenol. Cardiomyocyte sarcolemma integrity was significantly impaired in mdx but not in heterozygous and C57Bl/10 mice. Importantly, in vivo closed-chest hemodynamic assays revealed normal left ventricular function in {beta}-isoproterenol-stimulated heterozygous mice. Since the expression profile in the heterozygous mice mimicked viral transduction, we conclude that gene therapy correction in 50% of the heart cells may be sufficient to treat cardiomyopathy in mdx mice. This finding may also apply to the gene therapy of other inherited cardiomyopathies.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Khairallah, R. J. Khairallah, M. E. Young, B. G. Allen, M. A. Gillis, G. Danialou, C. F. Deschepper, B. J. Petrof, and C. Des Rosiers
Sildenafil and cardiomyocyte-specific cGMP signaling prevent cardiomyopathic changes associated with dystrophin deficiency
PNAS, May 13, 2008; 105(19): 7028 - 7033.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
C. Jung, A. S. Martins, E. Niggli, and N. Shirokova
Dystrophic cardiomyopathy: amplification of cellular damage by Ca2+ signalling and reactive oxygen species-generating pathways
Cardiovasc Res, March 1, 2008; 77(4): 766 - 773.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
B. Bostick, Y. Yue, C. Long, and D. Duan
Prevention of Dystrophin-Deficient Cardiomyopathy in Twenty-One-Month-Old Carrier Mice by Mosaic Dystrophin Expression or Complementary Dystrophin/Utrophin Expression
Circ. Res., January 4, 2008; 102(1): 121 - 130.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
J. S. Chamberlain, J. Metzger, M. Reyes, D. Townsend, and J. A. Faulkner
Dystrophin-deficient mdx mice display a reduced life span and are susceptible to spontaneous rhabdomyosarcoma
FASEB J, July 1, 2007; 21(9): 2195 - 2204.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
D. Duan
Challenges and opportunities in dystrophin-deficient cardiomyopathy gene therapy
Hum. Mol. Genet., October 15, 2006; 15(suppl_2): R253 - R261.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
P. M. L. Janssen, N. Hiranandani, T. A. Mays, and J. A. Rafael-Fortney
Utrophin deficiency worsens cardiac contractile dysfunction present in dystrophin-deficient mdx mice
Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2373 - H2378.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.