Zfy genes are required for efficient meiotic sex chromosome inactivation (MSCI) in spermatocytes

During spermatogenesis, germ cells that fail to synapse their chromosomes or fail to undergo meiotic sex chromosome inactivation (MSCI) are eliminated via apoptosis during mid-pachytene. Previous work showed that Y-linked genes Zfy1 and Zfy2 act as “executioners” for this checkpoint, and that wrongful expression of either gene during pachytene triggers germ cell death. Here, we show that in mice, Zfy genes are also necessary for efficient MSCI and the sex chromosomes are not correctly silenced in Zfy-deficient spermatocytes. In addition to this microarray data set, qPCR and RNA FISH data were used to confirm that MSCI is leaky in males lacking Zfy genes. The array data demonstrates that transgenic restoration of Zfy2 corrects the MSCI leakage phenotype. The associated RNA FISH data demonstrates that Zfy1 and Zfy2 are both able to correct the leakage phenotype. This experiment compares testis gene expression at 17.5 days post partum from XEO,Sry males (lacking all Y genes except Sry and Eif2s3y) with XE,Z2O,Sry males in which Zfy2 has been transgenically restored (n = 4 per genotype).