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Titolo:
Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2
Autore:
Mankodi, A; Urbinati, CR; Yuan, QP; Moxley, RT; Sansone, V; Krym, M; Henderson, D; Schalling, M; Swanson, MS; Thornton, CA;
Indirizzi:
Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA Univ Rochester Rochester NY USA 14642 ept Neurol, Rochester, NY 14642 USA Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Ctr Gene Therapy, Gainesville, FL 32610 USA Univ Florida Gainesville FL USA 32610 Therapy, Gainesville, FL 32610 USA Univ Florida, Coll Med, Ctr Mammalian Genet, Gainesville, FL 32610 USA Univ Florida Gainesville FL USA 32610 an Genet, Gainesville, FL 32610 USA Karolinska Hosp, Neurogenet Unit, Dept Mol Med, S-17176 Stockholm, Sweden Karolinska Hosp Stockholm Sweden S-17176 Med, S-17176 Stockholm, Sweden
Titolo Testata:
HUMAN MOLECULAR GENETICS
fascicolo: 19, volume: 10, anno: 2001,
pagine: 2165 - 2170
SICI:
0964-6906(20010915)10:19<2165:MLTNFO>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
EXPANDED CUG REPEAT; TRINUCLEOTIDE REPEAT; BINDING PROTEIN; CTG REPEAT; MYOPATHY; EXPANSION; MICE; CATARACTS; GENE; FORM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Thornton, CA Univ Rochester, Sch Med & Dent, Dept Neurol, 601 Elmwood Ave,Rochester, NY 14642 USA Univ Rochester 601 Elmwood Ave Rochester NY USA 14642 642 USA
Citazione:
A. Mankodi et al., "Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2", HUM MOL GEN, 10(19), 2001, pp. 2165-2170

Abstract

The phenotypes in myotonic dystrophy types 1 and 2 (DM1 and DM2) are similar, suggesting a shared pathophysiologic mechanism. DM1 is caused by expansion of a CTG repeat in the DMPK gene. Pathogenic effects of this mutation are likely to be mediated, at least in part, by the expanded CUG repeat in mutant mRNA. The mutant transcripts are retained in the nucleus in multiple discrete foci. We investigated the possibility that DM2 is also caused by expansion of a CTG repeat or related sequence. Analysis of DNA by repeat expansion detection methods, and RNA by ribonuclease protection, did not show an expanded CTG or CUG repeat in DM2. However, hybridization of muscle sections with fluorescence-labeled CAG-repeat oligonucleotides showed nuclear foci in DM2 similar to those seen in DM1. Nuclear foci were present in all patients with symptomatic DM1 (n = 9) or DM2 (n = 9) but not in any disease controls or healthy subjects (n = 23). The foci were not seen with CUG- or GUC-repeat probes. Foci in DM2 were distinguished from DM1 by lower stability of the probe-target duplex, suggesting that a sequence related to the DM1 CUG expansion accumulates in the DM2 nucleus. Muscleblind proteins, whichinteract with expanded CUG repeats in vitro, localized to the nuclear fociin both DM1 and DM2. These results support the idea that nuclear accumulation of mutant RNA is pathogenic in DM1, suggest that a similar disease process occurs in DM2, and point to a role for muscleblind in the pathogenesis of both disorders.

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Documento generato il 03/07/20 alle ore 16:46:08