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dc.contributor.authorSpring, K
dc.contributor.authorCross, S
dc.contributor.authorLi, C
dc.contributor.authorWatters, D
dc.contributor.authorBen-Senior, L
dc.contributor.authorWaring, P
dc.contributor.authorAhangari, F
dc.contributor.authorLu, SL
dc.contributor.authorChen, P
dc.contributor.authorMisko, I
dc.contributor.authorPaterson, C
dc.contributor.authorKay, G
dc.contributor.authorSmorodinsky, NI
dc.contributor.authorShiloh, Y
dc.contributor.authorLavin, MF
dc.date.accessioned2017-05-03T12:20:07Z
dc.date.available2017-05-03T12:20:07Z
dc.date.issued2001
dc.date.modified2007-10-23T07:51:42Z
dc.identifier.issn0008-5472
dc.identifier.urihttp://hdl.handle.net/10072/15494
dc.description.abstractATM, 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.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Association for Cancer Research
dc.publisher.placeBirmingham, Alabama, USA
dc.relation.ispartofpagefrom4561
dc.relation.ispartofpageto4568
dc.relation.ispartofissue11
dc.relation.ispartofjournalCancer Research
dc.relation.ispartofvolume61
dc.subject.fieldofresearchOncology and carcinogenesis
dc.subject.fieldofresearchcode3211
dc.titleAtm knock-in mice harboring an in-frame deletion corresponding to the human ATM 7636del9 common mutation exhibit a variant phenotype
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2001
gro.hasfulltextNo Full Text
gro.griffith.authorWatters, Dianne J.


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