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Titolo:
A targeted mouse Brca1 mutation removing the last BRCT repeat results in apoptosis and embryonic lethality at the headfold stage
Autore:
Hohenstein, P; Kielman, MF; Breukel, C; Bennett, LM; Wiseman, R; Krimpenfort, P; Cornelisse, G; van Ommen, GJ; Devilee, P; Fodde, R;
Indirizzi:
Leiden Univ, Med Ctr, Dept Human & Clin Genet, NL-2300 RA Leiden, Netherlands Leiden Univ Leiden Netherlands NL-2300 RA NL-2300 RA Leiden, Netherlands Leiden Univ, Med Ctr, Dept Pathol, NL-2300 RA Leiden, Netherlands Leiden Univ Leiden Netherlands NL-2300 RA NL-2300 RA Leiden, Netherlands NIEHS, Res Triangle Pk, NC 27709 USA NIEHS Res Triangle Pk NC USA 27709NIEHS, Res Triangle Pk, NC 27709 USA Netherlands Canc Inst, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands Netherlands Canc Inst Amsterdam Netherlands NL-1066 CX rdam, Netherlands
Titolo Testata:
ONCOGENE
fascicolo: 20, volume: 20, anno: 2001,
pagine: 2544 - 2550
SICI:
0950-9232(20010503)20:20<2544:ATMBMR>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
DNA-DAMAGE; BREAST-CANCER; TRANSCRIPTIONAL ACTIVATION; GENETIC INSTABILITY; TUMOR SPECTRUM; MEIOTIC CELLS; MODEL; EXPRESSION; REPAIR; MICE;
Keywords:
Brca1(1700T); mouse model; hereditary breast cancer; p53; genotype-phenotype correlation; DNA damage;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Fodde, R Leiden Univ, Med Ctr, Dept Human & Clin Genet, POB 9503, NL-2300 RA Leiden, Netherlands Leiden Univ POB 9503 Leiden Netherlands NL-2300 RA , Netherlands
Citazione:
P. Hohenstein et al., "A targeted mouse Brca1 mutation removing the last BRCT repeat results in apoptosis and embryonic lethality at the headfold stage", ONCOGENE, 20(20), 2001, pp. 2544-2550

Abstract

A mouse model with a targeted mutation in the 3' end of the endogenous Brca1 gene, Brca1(1700T), was generated to compare the phenotypic consequencesof truncated SI cal proteins with other mutant Brca1 models reported in the literature to date. Mice heterozygous for the Brca1(1700T) mutation do not show any predisposition to tumorigenesis, Treatment of these mice with ionizing radiation or breeding with Ape, Msh-2 or Tp53 mutant mouse models did not show any change in the tumor phenotype, Like other Brca1 mouse models, the Brca1(1700T) mutation is embryonic lethal in homozygous state, However, homozygous Brca1(1700T) embryos reach the headfold stage but are delayedin their development and fail to turn. Thus, in contrast to Brca1(null) models, the mutant embryos do not undergo growth arrest leading to a developmental block at 6.5 dpc, but continue to proliferate and differentiate until9.5 dpc. Homozygous embryos die between 9.5-10.5 dpc due to massive apoptosis throughout the embryo. These results indicate that a C-terminal truncating Brca1 mutation removing the last BRCT repeat has a different effect on normal cell function than does the complete absence of Brca1.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 08:54:55