Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Dramatic, expansion-biased, age-dependent, tissue specific somatic mosaicism in a transgenic mouse model of triplet repeat instability
Autore:
Fortune, MT; Vassilopoulos, C; Coolbaugh, MI; Siciliano, MJ; Monckton, DG;
Indirizzi:
Univ Glasgow, Inst Biomed & Life Sci, Div Mol Genet, Anderson Coll, Glasgow G11 6NU, Lanark, Scotland Univ Glasgow Glasgow Lanark Scotland G11 6NU ow G11 6NU, Lanark, Scotland Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 tr, Dept Mol Genet, Houston, TX 77030 USA
Titolo Testata:
HUMAN MOLECULAR GENETICS
fascicolo: 3, volume: 9, anno: 2000,
pagine: 439 - 445
SICI:
0964-6906(20000212)9:3<439:DEATSS>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
CONGENITAL MYOTONIC-DYSTROPHY; MACHADO-JOSEPH-DISEASE; EXPANDED CAG REPEATS; CTG REPEAT; TRINUCLEOTIDE REPEAT; (CTG)(N) REPEAT; IN-VITRO; MICE; GENE; HETEROGENEITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Monckton, DG Univ Glasgow, Inst Biomed & Life Sci, Div Mol Genet, AndersonColl, 56 Dumbarton Rd, Glasgow G11 6NU, Lanark, Scotland Univ Glasgow 56 Dumbarton Rd Glasgow Lanark Scotland G11 6NU
Citazione:
M.T. Fortune et al., "Dramatic, expansion-biased, age-dependent, tissue specific somatic mosaicism in a transgenic mouse model of triplet repeat instability", HUM MOL GEN, 9(3), 2000, pp. 439-445

Abstract

Myotonic dystrophy type 1 (DM1) is one of a growing number of inherited human diseases whose molecular basis has been implicated as the expansion of a trinucleotide DNA repeat. Expanded disease-associated alleles of >50 CTG repeats are unstable in both the germline and soma, Expansion of the unstable alleles over time and variation of the level of mutation between the somatic tissues of an individual are thought to account at least partially forthe tissue specificity and progressive nature of the symptoms. We previously generated a number of transgenic mouse lines containing a large expandedCTG repeat tract that replicated a number of the features of unstable DNA in humans, including frequent sex-specific changes in allele length during intergenerational transmission. Small length change mutations were apparentin the somatic tissues of young mice in all of the lines generated, but the gross instability observed in human DM1 patients was not replicated. We now show that in one of the lines, Dmt-D, spectacular, expansion-biased, tissue-specific instability is observed in older mice. The highest levels of instability were detected in kidney with gains of >500 repeats, representinga tripling of allele length, in some cells. Mosaicism accumulated in an age-dependent manner, but the tissue specificity did not obviously correlate with cell turnover. Such gross somatic mosaicism was not observed in three other lines examined, further emphasizing a role for flanking DNA in modulating repeat stability.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/07/20 alle ore 21:06:00