X-inactivation of theStslocus in the mouse: an anomaly of the dosage compensation mechanism

Abstract

Summary: The behaviour of theX- andY-borneStslocus has been studied in male and female mice. There was considerable heterogeneity in STS activity between inbred mouse strains, with a four fold difference in activity between the highest (101/H) and lowest (Ju/Ct) activity strains, which can be interpreted in terms of allelic differences. In all inbred strains male STS levels were higher than those of female STS levels and in the majority of strains tested male STS levels were nearly twice as high as female levels. Reciprocal crosses between C3H/HeH and the STS-deficient substrain, C3H/An, demonstrated that activities of theX- andY-borne genes in males are essentially the same and this suggested that the lower STS level in females derives fromX-inactivation of the locus. The possibility that hormonal differences could instead be responsible for the lower activity in females was ruled out by the findings that (a) castration of males did not reduce their STS levels and (b) sex-reversed males,X/X Sxr, had STS levels typical of females. Final proof that the mouseStslocus can be subject to theX-inactivation process was provided by the observation thatXXfemales had STS levels that were only slightly (20%) higher than those ofXOfemales. The difference may indicate incomplete inactivation of the locus. Linkage data verifying the location ofStson the distal end of theXchromosome are provided.In total, the results of this study show that the murineStslocus can be subject to theX-inactivation process and this, together with the existence of functional loci of near-equal activities on theXandYchromosomes, results in an imbalance of STS levels between the sexes.X-inactivation does not therefore serve as a dosage compensation mechanism for theStslocus in the mouse. All of these findings were made in C3H/HeH mice or in animals carrying C3H/HeH functionalStsalleles, and it is pointed out that the diverse results previously obtained by other investigators may be attributable to their use of different strains and crosses between strains but could also be complicated by technical factors.