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

Abstract

To investigate whether the preferential expression of genes on the translocated X chromosome in female mice carrying the X-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 T16H Pgk-lb/+ Pgk-lb ♀ × +Pgk-la / Y ♂, embryos expressing both isozymic forms of PGK-1 in the epiblast, and only the maternally inherited Pgk-lb allele in extra-embryonic tissues, were assumed to be chromosomally balanced, heterozygous female embryos carrying the Searle's translocation (like the mother). The normal X chromosome in this cross carries a high-expression Xcec locus. At 6 days post-coitum (p.c.) both isozymes were equally expressed in the epiblast as expected if both X chromosomes are active, but by 7 days p.c. the PGK-1B contribution was significantly less than 50%, suggesting that X inactivation has occurred with a bias towards inactivation of the translocated X chromosome carrying the lower-expression Xce allele. By 8 days p.c. the situation was the reverse, with a Pgk-lb contribution of significantly more than 50%, and by 12½ days p.c. no Pgk-la expression 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 16X chromosome. Two 7-day p.c. embryos unexpectedly showed equal expression of both Pgk-1 alleles in both embryonic and extra-embryonic tissues; these were presumably chromosomally unbalanced embryos which had inherited from the mother both an active translocated 16X chromosome carrying Pgk-lb and an active normal X chromosome carrying Pgk-la. © 1983, Cambridge University Press. All rights reserved.