Dataset Information


A novel mouse model for ataxia-telangiectasia with a N-terminal mutation displays a behavioral defect and a low incidence of lymphoma but no increased oxidative burden.

ABSTRACT: Ataxia-telangiectasia (A-T) is a rare multi-system disorder caused by mutations in the ATM gene. Significant heterogeneity exists in the underlying genetic mutations and clinical phenotypes. A number of mouse models have been generated that harbor mutations in the distal region of the gene, and a recent study suggests the presence of residual ATM protein in the brain of one such model. These mice recapitulate many of the characteristics of A-T seen in humans, with the notable exception of neurodegeneration. In order to study how an N-terminal mutation affects the disease phenotype, we generated an inducible Atm mutant mouse model (Atm(tm1Mmpl/tm1Mmpl), referred to as A-T [M]) predicted to express only the first 62 amino acids of Atm. Cells derived from A-T [M] mutant mice exhibited reduced cellular proliferation and an altered DNA damage response, but surprisingly, showed no evidence of an oxidative imbalance. Examination of the A-T [M] animals revealed an altered immunophenotype consistent with A-T. In contrast to mice harboring C-terminal Atm mutations that disproportionately develop thymic lymphomas, A-T [M] mice developed lymphoma at a similar rate as human A-T patients. Morphological analyses of A-T [M] cerebella revealed no substantial cellular defects, similar to other models of A-T, although mice display behavioral defects consistent with cerebellar dysfunction. Overall, these results suggest that loss of Atm is not necessarily associated with an oxidized phenotype as has been previously proposed and that loss of ATM protein is not sufficient to induce cerebellar degeneration in mice.

SUBMITTER: Campbell A 

PROVIDER: S-EPMC5007607 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

Similar Datasets

2020-01-01 | S-EPMC7144915 | BioStudies
1000-01-01 | S-EPMC6077713 | BioStudies
2014-01-01 | S-EPMC6211587 | BioStudies
1000-01-01 | S-EPMC5833483 | BioStudies
2001-01-01 | S-EPMC5964944 | BioStudies
2012-01-01 | S-EPMC3283185 | BioStudies
2017-01-01 | S-EPMC5687068 | BioStudies
2013-01-01 | S-EPMC3538311 | BioStudies
1000-01-01 | S-EPMC3048124 | BioStudies
1998-01-01 | S-EPMC317258 | BioStudies