dc.contributor.author | Spring, K | |
dc.contributor.author | Cross, S | |
dc.contributor.author | Li, C | |
dc.contributor.author | Watters, D | |
dc.contributor.author | Ben-Senior, L | |
dc.contributor.author | Waring, P | |
dc.contributor.author | Ahangari, F | |
dc.contributor.author | Lu, SL | |
dc.contributor.author | Chen, P | |
dc.contributor.author | Misko, I | |
dc.contributor.author | Paterson, C | |
dc.contributor.author | Kay, G | |
dc.contributor.author | Smorodinsky, NI | |
dc.contributor.author | Shiloh, Y | |
dc.contributor.author | Lavin, MF | |
dc.date.accessioned | 2017-05-03T12:20:07Z | |
dc.date.available | 2017-05-03T12:20:07Z | |
dc.date.issued | 2001 | |
dc.date.modified | 2007-10-23T07:51:42Z | |
dc.identifier.issn | 0008-5472 | |
dc.identifier.uri | http://hdl.handle.net/10072/15494 | |
dc.description.abstract | ATM, the gene mutated in the human immunodeficiency disorder ataxia-telangiectasia (A-T), plays a central role in recognizing ionizing radiation damage in DNA and in controlling several cell cycle checkpoints. We describe here a murine model in which a nine-nucleotide in-frame deletion has been introduced into the Atm gene by homologous recombination followed by removal of the selectable marker cassette by Cre-loxP site-specific, recombination-mediated excision. This mouse, Abm-Delta SRI, was designed as a model of one of the most common deletion mutations (7636de19) found in A-T patients. The murine Atm deletion results in the loss of three amino acid residues (SRI; 2556-2558) but produces near full-length detectable Atm protein that lacks protein kinase activity. Radiosensitivity was observed in Atm-Delta SRI mice, whereas the immunological profile of these mice showed greater heterogeneity of T-cell subsets than observed in Atm(-/-) mice. The life span of Atm-Delta SRI mice was significantly longer than that of Atm(-/-) mice when maintained under nonspecific pathogen-free conditions. This can be accounted for by a lower incidence of thymic lymphomas in Atm-Delta SRI mice up to 40 weeks, after which time the animals died of other causes. The thymic lymphomas in Atm-Delta SRI mice were characterized by extensive apoptosis, which appears to be attributable to an increased number of cells expressing Fas ligand. A variety of other tumors including B-cell lymphomas, sarcomas, and carcinomas not seen in Atm(-/-) mice were observed in older Atm-Delta SRI animals. Thus, expression of mutant protein in Atm-Delta SRI knock-in mice gives rise to a discernibly different phenotype to Atm(-/-) mice, which may account for the heterogeneity seen in A-T patients with different mutations. | |
dc.description.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | American Association for Cancer Research | |
dc.publisher.place | Birmingham, Alabama, USA | |
dc.relation.ispartofpagefrom | 4561 | |
dc.relation.ispartofpageto | 4568 | |
dc.relation.ispartofissue | 11 | |
dc.relation.ispartofjournal | Cancer Research | |
dc.relation.ispartofvolume | 61 | |
dc.subject.fieldofresearch | Oncology and carcinogenesis | |
dc.subject.fieldofresearchcode | 3211 | |
dc.title | Atm knock-in mice harboring an in-frame deletion corresponding to the human ATM 7636del9 common mutation exhibit a variant phenotype | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
gro.date.issued | 2001 | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Watters, Dianne J. | |