Skip Navigation


Human Molecular Genetics Advance Access originally published online on June 9, 2004
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (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 ISI Web of Science
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 arrow Search for citing articles in:
ISI Web of Science (11)
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?

Human Molecular Genetics, 2004, Vol. 13, No. 15 1669-1675
DOI: 10.1093/hmg/ddh174
Human Molecular Genetics, Vol. 13, No. 15 © Oxford University Press 2004; all rights reserved

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

Yongping Yue1, Jeffrey W. Skimming2, Mingju Liu1, Tammy Strawn2 and Dongsheng Duan1,*

1Department of Molecular Microbiology and Immunology and 2Department of Child Health and Department of Medical Pharmacology and Physiology, The University of Missouri, School of Medicine, Columbia, MO 65212, USA

Received April 12, 2004; Accepted May 26, 2004

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 questioned whether dystrophin expression in half of the heart cells was sufficient to prevent stress-induced cardiomyopathy. Heart function of mdx mouse is normal in the absence of external stress. To determine the therapeutic effect, we challenged 3-month-old mice with ß-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 ß-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.

* To whom correspondence should be addressed at: Department of Molecular Microbiology and Immunology, The University of Missouri, School of Medicine, One Hospital Drive, Room M610G, MSB, Columbia, MO 65212, USA. Tel: +1 5738849584; Fax: +1 5738824287; Email: duand{at}missouri.edu


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
 Hum Mol GenetHome page
D. Li, C. Long, Y. Yue, and D. Duan
Sub-physiological sarcoglycan expression contributes to compensatory muscle protection in mdx mice
Hum. Mol. Genet., April 1, 2009; 18(7): 1209 - 1220.
[Abstract] [Full Text] [PDF]

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
 Eur J Heart FailHome page
S. Deng, B. Kulle, M. Hosseini, G. Schluter, G. Hasenfuss, L. Wojnowski, and A. Schmidt
Dystrophin-deficiency increases the susceptibility to doxorubicin-induced cardiotoxicity
Eur J Heart Fail, October 1, 2007; 9(10): 986 - 994.
[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.