Negamycin can restore dystrophin in mdx skeletal muscle

M. Arakawa, Y. Nakayama, T. Hara, M. Shiozuka, S. Takeda, K. Kaga, S. Kondo, S. Morita, T. Kitamura, R. Matsuda

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Rescuing nonsense mutations is of great scientific and clinical interest. In 1999, Barton-Davis et al. reported that gentamicin (GM), an aminoglycoside antibiotic that causes misreading of stop codons during translation, restored dystrophin function in the mdx mouse, an animal model of Duchenne-type muscular dystrophy (DMD), which results from a nonsense mutation in the dystrophin gene. Here we report that subcutaneous injection of a dipeptide antibiotic, negamycin (NM), also rescues mdx mice and restores dystrophin to skeletal muscle. Dystrophin expression in these mice was confirmed by immunohistochemistry and by Western blotting. NM also exhibited less toxicity than did GM. Mice survived after two weeks' administration of NM at doses 100 times higher than the minimum effective dose, whereas mice injected with similar levels of GM died within four hours after a single injection. These results suggest that NM might be a promising candidate for of DMD caused by nonsense mutations. NM may also provide a promising drug for correction of many other genetic diseases caused by nonsense mutations.

Original languageEnglish
Pages (from-to)154-158
Number of pages5
JournalActa Myologica
Volume20
Issue numberSEPT.
Publication statusPublished - Dec 1 2001
Externally publishedYes

Fingerprint

Dystrophin
Nonsense Codon
Skeletal Muscle
Gentamicins
Inbred mdx Mouse
Duchenne Muscular Dystrophy
Anti-Bacterial Agents
Inborn Genetic Diseases
Terminator Codon
Dipeptides
Aminoglycosides
Subcutaneous Injections
Animal Models
Western Blotting
Immunohistochemistry
negamycin
Injections
Pharmaceutical Preparations
Genes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Arakawa, M., Nakayama, Y., Hara, T., Shiozuka, M., Takeda, S., Kaga, K., ... Matsuda, R. (2001). Negamycin can restore dystrophin in mdx skeletal muscle. Acta Myologica, 20(SEPT.), 154-158.

Negamycin can restore dystrophin in mdx skeletal muscle. / Arakawa, M.; Nakayama, Y.; Hara, T.; Shiozuka, M.; Takeda, S.; Kaga, K.; Kondo, S.; Morita, S.; Kitamura, T.; Matsuda, R.

In: Acta Myologica, Vol. 20, No. SEPT., 01.12.2001, p. 154-158.

Research output: Contribution to journalArticle

Arakawa, M, Nakayama, Y, Hara, T, Shiozuka, M, Takeda, S, Kaga, K, Kondo, S, Morita, S, Kitamura, T & Matsuda, R 2001, 'Negamycin can restore dystrophin in mdx skeletal muscle', Acta Myologica, vol. 20, no. SEPT., pp. 154-158.
Arakawa M, Nakayama Y, Hara T, Shiozuka M, Takeda S, Kaga K et al. Negamycin can restore dystrophin in mdx skeletal muscle. Acta Myologica. 2001 Dec 1;20(SEPT.):154-158.
Arakawa, M. ; Nakayama, Y. ; Hara, T. ; Shiozuka, M. ; Takeda, S. ; Kaga, K. ; Kondo, S. ; Morita, S. ; Kitamura, T. ; Matsuda, R. / Negamycin can restore dystrophin in mdx skeletal muscle. In: Acta Myologica. 2001 ; Vol. 20, No. SEPT. pp. 154-158.
@article{e116014d3fcd44059e22e49b9c70e2f9,
title = "Negamycin can restore dystrophin in mdx skeletal muscle",
abstract = "Rescuing nonsense mutations is of great scientific and clinical interest. In 1999, Barton-Davis et al. reported that gentamicin (GM), an aminoglycoside antibiotic that causes misreading of stop codons during translation, restored dystrophin function in the mdx mouse, an animal model of Duchenne-type muscular dystrophy (DMD), which results from a nonsense mutation in the dystrophin gene. Here we report that subcutaneous injection of a dipeptide antibiotic, negamycin (NM), also rescues mdx mice and restores dystrophin to skeletal muscle. Dystrophin expression in these mice was confirmed by immunohistochemistry and by Western blotting. NM also exhibited less toxicity than did GM. Mice survived after two weeks' administration of NM at doses 100 times higher than the minimum effective dose, whereas mice injected with similar levels of GM died within four hours after a single injection. These results suggest that NM might be a promising candidate for of DMD caused by nonsense mutations. NM may also provide a promising drug for correction of many other genetic diseases caused by nonsense mutations.",
author = "M. Arakawa and Y. Nakayama and T. Hara and M. Shiozuka and S. Takeda and K. Kaga and S. Kondo and S. Morita and T. Kitamura and R. Matsuda",
year = "2001",
month = "12",
day = "1",
language = "English",
volume = "20",
pages = "154--158",
journal = "Acta Myologica",
issn = "1128-2460",
publisher = "Gaetano Conte Academy",
number = "SEPT.",

}

TY - JOUR

T1 - Negamycin can restore dystrophin in mdx skeletal muscle

AU - Arakawa, M.

AU - Nakayama, Y.

AU - Hara, T.

AU - Shiozuka, M.

AU - Takeda, S.

AU - Kaga, K.

AU - Kondo, S.

AU - Morita, S.

AU - Kitamura, T.

AU - Matsuda, R.

PY - 2001/12/1

Y1 - 2001/12/1

N2 - Rescuing nonsense mutations is of great scientific and clinical interest. In 1999, Barton-Davis et al. reported that gentamicin (GM), an aminoglycoside antibiotic that causes misreading of stop codons during translation, restored dystrophin function in the mdx mouse, an animal model of Duchenne-type muscular dystrophy (DMD), which results from a nonsense mutation in the dystrophin gene. Here we report that subcutaneous injection of a dipeptide antibiotic, negamycin (NM), also rescues mdx mice and restores dystrophin to skeletal muscle. Dystrophin expression in these mice was confirmed by immunohistochemistry and by Western blotting. NM also exhibited less toxicity than did GM. Mice survived after two weeks' administration of NM at doses 100 times higher than the minimum effective dose, whereas mice injected with similar levels of GM died within four hours after a single injection. These results suggest that NM might be a promising candidate for of DMD caused by nonsense mutations. NM may also provide a promising drug for correction of many other genetic diseases caused by nonsense mutations.

AB - Rescuing nonsense mutations is of great scientific and clinical interest. In 1999, Barton-Davis et al. reported that gentamicin (GM), an aminoglycoside antibiotic that causes misreading of stop codons during translation, restored dystrophin function in the mdx mouse, an animal model of Duchenne-type muscular dystrophy (DMD), which results from a nonsense mutation in the dystrophin gene. Here we report that subcutaneous injection of a dipeptide antibiotic, negamycin (NM), also rescues mdx mice and restores dystrophin to skeletal muscle. Dystrophin expression in these mice was confirmed by immunohistochemistry and by Western blotting. NM also exhibited less toxicity than did GM. Mice survived after two weeks' administration of NM at doses 100 times higher than the minimum effective dose, whereas mice injected with similar levels of GM died within four hours after a single injection. These results suggest that NM might be a promising candidate for of DMD caused by nonsense mutations. NM may also provide a promising drug for correction of many other genetic diseases caused by nonsense mutations.

UR - http://www.scopus.com/inward/record.url?scp=0035677466&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035677466&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0035677466

VL - 20

SP - 154

EP - 158

JO - Acta Myologica

JF - Acta Myologica

SN - 1128-2460

IS - SEPT.

ER -