三瀬 名丹

To clarify the sequence of events that ultimately achieves the nonrandom inactivation of the paternally inherited X chromosome in postpartum female mice heterozygous for T(X;16)16H, we set out to examine the expression of <i>Xist </i>alleles and the X-linked <i>HMG-lacZ</i> transgene in embryos recovered at the egg cylinder stage. Lack of expression of the <i>Xist<sup>b</sup></i> allele on the 16<sup>X</sup> translocation chromosome in the embryonic region of 7.5 d postcoitum (dpc) X<sup>16</sup>/X<sup>n</sup><i>Xist<sup>a</sup></i>;16<sup>X</sup><i>Xist<sup>b</sup></i>/16 embryos strongly suggested the occurrence of nonrandom inactivation in favor of the normal X chromosome. The simplest explanation would be biased choice, followed by postinactivation selection against genetically unbalanced cells. However, the frequency and distribution of β-galactosidase-positive cells in X<sup>16</sup>/X<sup>n</sup><i>lacZ</i>;16<sup>X</sup>/16 embryos at 6.5 and 7.5 dpc, together with earlier cytogenetic data, raised an intriguing possibility that the majority of 16<sup>X</sup> chromosomes were prevented from completing the inactivation process, when they had been chosen to be silenced. Phenotypes of female mice carrying a spontaneous recombination between X<sup>n</sup> and 16<sup>X</sup> in the segment defined by the T16H breakpoint and the X-linked <i>Ta </i>locus suggested that the nonrandomness was brought about by disruption of an X-chromosomal sequence or structure at the translocation breakpoint.