X-chromosome activity in female mouse embryos heterozygous forPgk-1and Searle's translocation, T(X; 16) 16H

Abstract

SUMMARYTo investigate whether the preferential expression of genes on the translocatedXchromosome in female mice carrying theX-autosome translocation T(X; 16)16H (Searle's translocation) is due to non-random inactivation or to cell selection, we examined tissues of mouse embryos heterozygous for the X-linked gene coding for phosphoglycerate kinase (Pgk-1). From the cross T16HPgk-lb/+Pgk-lb♀ × +Pgk-la/Y♂, embryos expressing both isozymic forms of PGK-1 in the epiblast, and only the maternally inheritedPgk-lballele in extra-embryonic tissues, were assumed to be chromosomally balanced, heterozygous female embryos carrying the Searle's translocation (like the mother). The normalXchromosome in this cross carries a high-expressionXceclocus. At 6 days post-coitum (p.c.) both isozymes were equally expressed in the epiblast as expected if bothXchromosomes are active, but by 7 days p.c. the PGK-1B contribution was significantly less than 50%, suggesting thatXinactivation has occurred with a bias towards inactivation of the translocatedXchromosome carrying the lower-expressionXceallele. By 8 days p.c. the situation was the reverse, with aPgk-lbcontribution of significantly more than 50%, and by 12½ days p.c. noPgk-laexpression could be detected. We interpret the dramatic change in isozy me expression between 7 and 8 days p.c. as indicating rapid selection against cells that had inactivated the translocated 16Xchromosome. Two 7-day p.c. embryos unexpectedly showed equal expression of bothPgk-1alleles in both embryonic and extra-embryonic tissues; these were presumably chromosomally unbalanced embryos which had inherited from the mother both an active translocated 16Xchromosome carryingPgk-lband an active normalXchromosome carryingPgk-la.