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Titolo:
Tk(+/-) mouse model for detecting in vivo mutation in an endogenous, autosomal gene
Autore:
Dobrovolsky, VN; Casciano, DA; Heflich, RH;
Indirizzi:
Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA Natl Ctr Toxicol Res Jefferson AR USA 72079 icol, Jefferson, AR 72079 USA
Titolo Testata:
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
fascicolo: 1-2, volume: 423, anno: 1999,
pagine: 125 - 136
SICI:
1386-1964(19990125)423:1-2<125:TMMFDI>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
ETHYL-N-NITROSOUREA; THYMIDINE KINASE LOCUS; LACI TRANSGENIC MICE; LYMPHOMA-CELLS; ADENINE PHOSPHORIBOSYLTRANSFERASE; MAMMALIAN-CELLS; SHUTTLE VECTORS; L5178Y/TK+/ MOUSE; ESCHERICHIA-COLI; INVIVO EXPOSURE;
Keywords:
thymidine kinase; knockout; N-ethyl-N-nitrosourea; mutation; 5-bromo-2 '-deoxyuridine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Dobrovolsky, VN Natlferson,xicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jef Natl Ctr Toxicol Res HFT-120,3900 NCTR Rd Jefferson AR USA 72079
Citazione:
V.N. Dobrovolsky et al., "Tk(+/-) mouse model for detecting in vivo mutation in an endogenous, autosomal gene", MUT RES-F M, 423(1-2), 1999, pp. 125-136

Abstract

Tk(+/-) transgenic mice were created using an embryonic stem cell line in which one allele of the endogenous thymidine kinase (Tk) gene was inactivated by;targeted homologous recombination. Breeding Tk(+/-) parents produced viable Tk(-/-) knockout (KO) mice. Splenic lymphocytes from KO mice were used in reconstruction experiments for determining the conditions necessary for recovering Tk somatic cell mutants from Tk(+/-) mice. The cloning efficiency of KO lymphocytes was not affected by the toxic thymidine analogues 5-bromo-2'-deoxyuridine (BrdUrd) or trifluorothymidine (TFT), or by BrdUrd inthe presence of lymphocytes from Tk(+/-) animals; however, it was easier to identify clones resistant to BrdUrd than to TFT when Tk(+/-) cells were present. Tk(+/-) mice were treated with vehicle or 100 mg/kg of N-ethyl-N-nitrosourea (ENU), and after 4 months, the frequency of Tk mutant lymphocyteswas measured by resistance to BrdUrd. The frequency of Tk mutants was 22 +/- 5.9 X 10(-6) in control animals and 80 +/- 31 X 10(-6) in treated mice. In comparison, the frequency of Hprt mutant lymphocytes, as measured by resistance to 6-thioguanine, was 2.0 +/- 1.2 X 10(-6) in control animals and 84 +/- 28 X 10(-6) in the ENU-treated mice. Analysis of BrdUrd-resistant lymphocyte clones derived from the ENU-treated animals revealed point mutations in the non-targeted Tk allele. These results indicate that the selection of BrdUrd-resistant lymphocytes from Tk(+/-) mice may be used for assessingin vivo mutation in an endogenous, autosomal gene. (C) 1999 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 16:19:53