Attempt to rescue sex-reversal by transgenic expression of the PISRT1 gene in XX PIS-/- goats

作者：Boulanger L; Kocer A; Daniel N; Pannetier M; Chesne P; Heyman Y; Renault L; Mandon Pepin B; Chavatte Palmer P; Vignon X; Vilotte J L; Cotinot C; Renard J P; Pailhoux E^*

来源：Sexual Development, 2008, 2(3): 142-151.

DOI：10.1159/000143432

• goat cloning
• nuclear transfer
• PIS locus
• sex determination
• XX sex-reversal

The Polled Intersex Syndrome (PIS mutation) in goats leads to an absence of horn and to an early sex-reversal of the XX gonads. This mutation is a deletion of an 11.7-kb DNA fragment showing a tissue-specific regulatory activity. Indeed, in XX PIS-/- gonads the deletion of PIS leads to the transcriptional extinction of at least 3 neighboring genes, FOXL2, PFOXic and PISRT1. Among them, only FOXL2 is a 'classical' gene, encoding a highly conserved transcription factor. On the other hand, knock-out of Foxl2 in mice results in an early blocking of follicle formation without sex-reversal. This phenotype discrepancy leads to two hypotheses, either FOXL2 is responsible for XX sex-reversal in goat assuming distinct functions of its protein during ovarian differentiation in different mammals, or other PIS-regulated genes are involved. To assess the second possibility, PISRT1 expression was constitutively restored in XX PIS-/- gonads. Six transgenic fetuses were obtained by nuclear transfer and studied at 2 developmental stages, 41 and 46 days post-reconstruction. The gonads of these fetuses appear phenotypically identical to those of cloned non-transgenic controls. Conclusively, this result argues for FOXL2 being responsible for the PIS gonadassociated phenotype. Its invalidation in goat will help to better understand this complex syndrome.

• 出版日期2008