Upregulation of FasL and apoptosis in thymic lymphomas in Atm knock-in mice

Lavin, MF and Spring, K (2002) Upregulation of FasL and apoptosis in thymic lymphomas in Atm knock-in mice. Toxicology, 181 483-489. doi:10.1016/S0300-483X(02)00462-6


Author Lavin, MF
Spring, K
Title Upregulation of FasL and apoptosis in thymic lymphomas in Atm knock-in mice
Journal name Toxicology   Check publisher's open access policy
ISSN 0300-483X
Publication date 2002-01-01
Sub-type Article (original research)
DOI 10.1016/S0300-483X(02)00462-6
Volume 181
Start page 483
End page 489
Total pages 7
Place of publication Clare
Publisher Elsevier Sci Ireland Ltd
Language eng
Abstract Several members of the phosphatidylinositol 3-kinase family play key roles in recognising and responding to damage in DNA, induced by a variety of chemicals and other agents. One of these, ATM, the product of the gene mutated in the human genetic disorder ataxia-telangiectasia (A-T), recognises double strand breaks in DNA caused by ionizing radiation and radiomimetic chemicals. In order to study DNA damage recognition and the abnormalities of genome instability and cancer predisposition that occur in A-T patients, we generated a mouse model expressing a mutant form of Atm corresponding to a common human mutation. In this model, a 9 nucleotide in-frame deletion was introduced into the Atm gene and has been designated Atm-DeltaSRI. These animals had a longer lifespan than Atm gene disrupted mice (Atm(-/-)) and they developed less thymic lymphomas. A characteristic of the lymphomas appearing in Atm-ASRI mice was an increased rate of apoptosis compared to the corresponding tumours in Atm(-/-) mice. Increased expression of FasL in these tumours may account for the higher levels of apoptosis. These results demonstrate that expression of mutant Atm in mice gives rise to phenotypic differences compared to Atm(-/-) mice and has implications for heterogeneity described in the human syndrome. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
Keyword Pharmacology & Pharmacy
Toxicology
apoptosis
FasL
knock-in mice
thymic lymphomas
Atm
Ataxia-telangiectasia Gene
Double-strand Breaks
Ionizing-radiation
Deficient Mice
Activation
Damage
Phosphorylation
Product
Cells
Hypersensitivity
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Wed, 17 Oct 2007, 21:49:42 EST