Summary
ATR-X syndrome is the first human genetic disease known to be caused by mutations in a chromatin remodelling factor. At present we do not know how ATRX influences gene expression or what effect it has on cell behaviour. Nevertheless, we have previously noted that none of the natural mutations causing ATR-X syndrome are nulls, which suggests that it plays a critical role in normal development. Results of conditional inactivation of Atrx in the developing mouse forebrain, based on the Atrx flox allele described here, shows that Atrx exerts a major effect on terminally differentiating neurons. Conditional inactivation of Atrx in other tissues is underway. Here we have shown that animal-wide disruption of the Atrx gene causes a severe embryonic-lethal phenotype, revealing an essential role for Atrx in the formation of the murine trophoblast. In addition, Atrx appears to escape imprinted X-chromosome inactivation in the extraembryonic tissues of some carrier female mice.