The role of the ataxia - telangiectasia mutated protein in bone development

Abstract

ATM stands for Ataxia Telangiectasia Mutated. Mutations of this gene in humans results in the rare genetic disorder, Ataxia -Telangiectasia. ATM functions as a DNA damage sensor and a checkpoint control protein. In response to DNA damage, ATM and other checkpoint proteins such as c-Abl and p53 initiate a complex signal transduction cascade to halt the cell cycle and facilitate repair. A-T patients are predisposed to developing cancer due to non-functional ATM, and also show premature aging, sterility, diabetes, and growth defects. Most of these features are recapitulated in the Atm-/- mice. Knockout mice of Atm downstream targets p53 and c-Abl both exhibit aberrant bone development. In vivo and in vitro studies of Atm-/- mice indicate accelerated bone resorption, compromised bone formation and hypogonadism. This is the first link between Atm deficiency and steroid hormone shortage. The female Atm-/- mouse could be a potential animal model for post a?? menopausal osteoporosis.