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this study has revealed an unexpected role for Atrx in the murine trophectoderm, as a result of the early lethality observed in Atrxnull embryos it is not possible to rule out other roles for Atrx at later developmental stages in tissues of the embryo proper. Indeed, we show that Atrx is highly expressed throughout the entire developing embryo at 7.5 dpc (Figure 5B), and it is likely that Atrx function will turn out to be important for other differentiating tissues. Tetraploid aggregation experiments (in which mutant embryos are rescued with wild-type extraembryonic tissues) might shed more light on the role of Atrx during later mouse development, but these issues can be more subtly dissected by combining the conditional Atrx flox allele that we have generated with different tissue-specific Cre transgenes. As mentioned above, this approach has already revealed a critical role for Atrx during neuronal differentiation in adult mice [20]. Further evidence that Atrx is also required at later stages of mouse development is provided by the observed dramatic skewing against Atrx-negative cells in some somatic tissues of carrier female mice, whose tissues initially comprise a mosaic of Atrx-positive and Atrx-negative cells as a result of random X-inactivation (M. Muers, personal communication)."}

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