Aberrant Xinactivation

In mice, the parental origin of a supernumerary X chromosome is of the utmost importance in assessing the viability of the embryo; XmXmY embryos have only been observed in rare circumstances,94 whereas XmXpY embryos are fairly common.95 Analysis of embryos disomic for the maternal X chromosome (XmXmXp; XmXmY) further demonstrates that a supernumerary Xm is embryonic lethal,96'97 largely due to failure of extraembryonic tissues to develop. Embryonic tissues, in contrast, develop relatively well until approximately E7 when a lack of mesoderm becomes apparent.98 Cumulatively, these findings indicate that aberrant X-chromosome inacti-vation is responsible for embryonic lethality and/or extreme developmental anomalies.

Aberrant gene silencing, either of autosomally-imprinted genes or of X-linked genes, has also been demonstrated to occur in aging mammalian individuals.99 Interestingly, skewed X-chromosome inactivation is also found to occur increasingly with age,100 as well as in recurrent loss of pregnancy,101-103 trisomic pregnancy,104 and in the progression of cancers.105-107

Was this article helpful?

0 0

Post a comment