The appropriateness of the mouse model for ataxia-telangiectasia: Neurological defects but no neurodegeneration

Patients with ataxia-telangiectasia (A-T) are characterised by genome instability, cancer predisposition and a progressive neurodegeneration. A number of model systems have been developed for A-T but none recapitulate all the phenotype. The majority of these models have been generated in mice. While Atm deficient mouse models exhibit much of the phenotype described in patients with A-T, the broad consensus is that they do not display the most debilitating aspect of A-T, i.e. neurodegeneration. Cerebellar atrophy is one of the neuronal characteristics of A-T patients due to defects in neuronal development and progressive loss of Purkinje and granule cells. This is not evident in Atm-deficient mutants but there are multiple reports on neurological abnormalities in these mice. The focus of this review is to evaluate the appropriateness of Atm mutant mouse models for A-T, particularly with reference to neurological abnormalities and how they might relate to neurodegeneration. (C) 2013 Elsevier B.V. All rights reserved.