Paternal deletion of the antisense promoter in mice results in derepression of Nesp55 in cis, thereby leading to biallelic expression of the latter [96]. This finding indicates that at least one of the roles of the antisense transcript is to silence the paternal Nesp55 promoter. However, the effect of the deletion of the antisense promoter is not limited to Nesp55 expression. First, the deleted region evidently comprises an enhancer of the XLαs promoter, resulting in a dramatic reduction in XLαs expression and, thus, a phenotype similar to that observed in Gnasxl knockout mice. Second, mice with the paternal deletion exhibit a modest decrease in A/B expression combined with an increase in the methylation of the A/B promoter. Third, in those tissues where Gsα is normally silenced from the paternal allele, the diminished A/B expression is associated with an increase in Gsα expression in cis, i.e. the tissue specific Gsα imprinting is relaxed. These findings clearly demonstrate the importance of the antisense transcript in the regulation of imprinted gene expression from the GNAS locus. Nonetheless, what causes the reduction of paternal
