Efficient utrophin expression following adenovirus gene transfer in dystrophic muscle

Biochemical and Biophysical Research Communications
R GilbertG Karpati

Abstract

Utrophin is a homologue of dystrophin, the protein whose absence is responsible for Duchenne muscular dystrophy (DMD). As a first step toward clarifying if adenovirus (AV)-mediated utrophin transfer is a possible option to treat DMD, we have constructed an AV expressing utrophin (AdCMV-Utr) and studied utrophin expression after intramuscular injection of mdx mice, the mouse DMD model. Overexpression of utrophin by AdCMV-Utr was marked and nontoxic. The recombinant utrophin was distributed homogeneously at the surface of the muscle fibers. Its expression was sufficient to restore the normal histochemical pattern of alpha-sarcoglycan and beta-dystroglycan at this site. These two proteins are members of the dystrophin associated protein complex whose distribution is greatly reduced at the surface of the DMD muscle. These data indicate that AV-mediated utrophin transfer is an efficient way of utrophin upregulation in muscle and has the potential of becoming a treatment for DMD.

References

Oct 1, 1989·Muscle & Nerve·S C WatkinsL M Kunkel
Mar 1, 1993·Journal of Neuropathology and Experimental Neurology·G KarpatiP Holland
Apr 16, 1996·Proceedings of the National Academy of Sciences of the United States of America·N DeconinckJ M Gillis
Jan 1, 1997·Nature Medicine·G Karpati

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Citations

Jun 18, 2002·Journal of Cellular and Molecular Medicine·G M SmytheM D Grounds
Mar 20, 2002·Current Neurology and Neuroscience Reports·P R Clemens, F J Duncan
Sep 11, 2002·Neuromuscular Disorders : NMD·Dominic J Wells, Kim E Wells
Dec 15, 2000·Progress in Pediatric Cardiology·N E BowlesJ A Towbin
May 20, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tirsa L E van WesteringMatthew J A Wood
Mar 12, 2013·Expert Opinion on Drug Discovery·Catherine Moorwood, Tejvir S Khurana
Dec 19, 2003·Expert Opinion on Biological Therapy·Regina Lee Sohn, Emanuela Gussoni
Mar 5, 2016·American Journal of Human Genetics·Kay E Davies
Mar 7, 2007·The International Journal of Biochemistry & Cell Biology·Nathalie DanièleMarc Bartoli
May 3, 2015·Human Molecular Genetics·Simon GuiraudKay E Davies
Nov 13, 2001·Developmental Cell·P SealeM A Rudnicki
Aug 2, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jatinderpal R DeolGeorge Karpati
Apr 11, 2000·Microscopy Research and Technique·A O GramoliniB J Jasmin
Oct 4, 2003·Nature Reviews. Genetics·Judith C T van Deutekom, Gert-Jan B van Ommen
Oct 18, 2001·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·S Takeda, Y Miyagoe-Suzuki
Mar 28, 2002·Physiological Reviews·Derek J BlakeKay E Davies
Jun 1, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Joe V ChakkalakalBernard J Jasmin
Jun 21, 2005·The Biochemical Journal·Armelle Bonet-KerracheCécile Gauthier-Rouvière

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