Loss of the ataxia-telangiectasia gene product causes oxidative damage in target organs.

Barlow C, Dennery PA, Shigenaga MK, Smith MA, Morrow JD, Roberts LJ, Wynshaw-Boris A, Levine RL
Proc Natl Acad Sci U S A. 1999 96 (17): 9915-9

PMID: 10449794 · PMCID: PMC22310 · DOI:10.1073/pnas.96.17.9915

Ataxia-telangiectasia (A-T) is characterized by a markedly increased sensitivity to ionizing radiation, increased incidence of cancer, and neurodegeneration, especially of the cerebellar Purkinje cells. Ionizing radiation oxidizes macromolecules and causes tissue damage through the generation of reactive oxygen species (ROS). We therefore hypothesized that A-T is due to oxidative damage resulting from loss of function of the A-T gene product. To assess this hypothesis, we employed an animal model of A-T, the mouse with a disrupted Atm gene. We show that organs which develop pathologic changes in the Atm-deficient mice are targets of oxidative damage, and that cerebellar Purkinje cells are particularly affected. These observations provide a mechanistic basis for the A-T phenotype and lay a rational foundation for therapeutic intervention.

MeSH Terms (18)

Animals Ataxia Telangiectasia Ataxia Telangiectasia Mutated Proteins Cell Cycle Proteins DNA-Binding Proteins Heme Oxygenase (Decyclizing) Heme Oxygenase-1 Isoenzymes Lipid Metabolism Membrane Proteins Mice Mice, Knockout Oxidation-Reduction Oxidative Stress Protein-Serine-Threonine Kinases Proteins Purkinje Cells Tumor Suppressor Proteins

Connections (1)

This publication is referenced by other Labnodes entities:

Links