Tsixtricks

X-chromosome inactivation (XCI) is controlled by expression of the Tsix gene and its regulation of Xist mRNA accumulation. Deleting one copy of Tsix results in skewed XCI towards the mutated X chromosome in female soma. In an Advanced Online Publication in Nature Genetics, Jeannie Lee reports the generation of homozygous Tsix-null mice by breeding heterozygote animals (Nature Genetics, 29 July 2002, doi:10.1038/ng939). The frequency of homozygote offspring was 20-40% of that expected. Furthermore, homozygous mutation caused a significant sex-ratio distortion favouring male births. Homozygous null females had extremely low fertility and were often sterile. The sex-ratio distortion seems to be linked to female-specific defects in trophoblast and inner cell mass (ICM) growth. Lee generated hybrid mice with polymorphic X chromosomes to monitor XCI. She demonstrated that the loss of both copies of Tsixrandomizes XCI. Lee proposes a "chaotic" choice model to explain these observations.