Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
A zinc finger truncation of murine WT1 results in the characteristic urogenital abnormalities of Denys-Drash syndrome
Autore:
Patek, CE; Little, MH; Fleming, S; Miles, C; Charlieu, JP; Clarke, AR; Miyagawa, K; Christie, S; Doig, J; Harrison, DJ; Porteous, DJ; Brookes, AJ; Hooper, ML; Hastie, ND;
Indirizzi:
Western Gen Hosp, MRC, Genet Unit, Edinburgh EH4 2XU, Midlothian, ScotlandWestern Gen Hosp Edinburgh Midlothian Scotland EH4 2XU dlothian, Scotland Univ Queensland, Ctr Mol & Cellular Biol, St Lucia, Qld 4072, Australia Univ Queensland St Lucia Qld Australia 4072 St Lucia, Qld 4072, Australia Univ,Edinburgh, Western Gen Hosp, Sir Alastair Currie CRC Labs, Mol Med Ctr Univ Edinburgh Edinburgh Midlothian Scotland EH4 2XU RC Labs, Mol Med Ctr Univnddinburgh, Sch Med, Dept Pathol, Edinburgh EH8 9AG, Midlothian, Scotla Univ Edinburgh Edinburgh Midlothian Scotland EH8 9AG , Midlothian, Scotla
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 6, volume: 96, anno: 1999,
pagine: 2931 - 2936
SICI:
0027-8424(19990316)96:6<2931:AZFTOM>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
WILMS-TUMOR GENE; SUBNUCLEAR LOCALIZATION; STEM-CELLS; MOUSE; EXPRESSION; PROTEIN; MUTATIONS; FERTILITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Hastie, ND Western Gen Hosp, MRC, Genet Unit, Crewe Rd, Edinburgh EH4 2XU,Midlothian, Western Gen Hosp Crewe Rd Edinburgh Midlothian Scotland EH4 2XU
Citazione:
C.E. Patek et al., "A zinc finger truncation of murine WT1 results in the characteristic urogenital abnormalities of Denys-Drash syndrome", P NAS US, 96(6), 1999, pp. 2931-2936

Abstract

The Wilms tumor-suppressor gene, WT1, plays a key role in urogenital development, and WT1 dysfunction is implicated in both neoplastic (Wilms tumor, mesothelioma, leukemias, and breast cancer) and nonneoplastic (glomerulosclerosis) disease. The analysis of diseases linked specifically with WT1 mutations, such as Denys-Drash syndrome (DDS), can provide valuable insight concerning the role of WT1 in development and disease. DDS is a rare childhooddisease characterized by a nephropathy involving mesangial sclerosis, XY pseudohermaphroditism, and/or Wilms tumor (WT). DDS patients are constitutionally heterozygous for exonic point mutations in WT1, which include mutations predicted to truncate the protein within the C-terminal zinc finger (ZF)region. We report that heterozygosity for a targeted murine Wt1 allele, Wt1(tmT396), which truncates ZF3 at codon 396, induces mesangial sclerosis characteristic of DDS in adult heterozygous and chimeric mice. Male genital defects also were evident and there was a single case of Wilms tumor in which the transcript of the nontargeted allele showed an exon 9 skipping event,implying a causal link between Wt1 dysfunction and Wilms tumorigenesis in mice. However, the mutant WT1(tmT396) protein accounted for only 5% of WT1 in both heterozygous embryonic stem cells and the WT. This has implicationsregarding the mechanism by which the mutant allele exerts its effect.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 17:32:11