Curtin, Maureen2013-11-072013-11-0720092009Source: Masters Abstracts International, Volume: 49-02, page: 1170.http://hdl.handle.net/10393/28512http://dx.doi.org/10.20381/ruor-19307ATR-X syndrome (OMIM# 30032) is a form of mental retardation that arises from mutations in the ATRX gene in humans. Affected individuals often exhibit severe mental retardation, unique facial dysmorphy, psychomotor impairments and urogential abnormalities. ATRX itself is a SWI/SNF-like chromatin remodeling protein whose role in development is not yet fully understood. To study the role of ATRX in the brain, a conditional forebrain knockout model is used. Reduced forebrain size, impaired development/disorganization of the cortex and enhanced apoptosis of cortical progenitors upon differentiation are observed in this Atrxnull model. In this study, we show that the conditional knockout of Atrx in the murine cortex results in the increased activation of Parp-1, most strikingly during early corticogenesis. An increase in DNA damage, as determined by higher levels of gammaH2AX, is also present during this time. This is consistent with the well-characterized role of Parp-1 activation in response to DNA damage. Furthermore, we demonstrate that there is a severe loss of layer V Er81+ neurons in the Atrxnull cortex. Loss of Er81+ neurons is associated with impaired motor skills, which is a common feature of ATR-X patients.95 p.enChemistry, Biochemistry.Thesis