Attempt to Rescue Sex-Reversal by Transgenic Expression of the PISRT1 Gene in XX PIS–/– Goats

Authors:
  • AKA. Kocer
    A. Kocer
  • NDN. Daniel
    N. Daniel
  • MPM. Pannetier
    M. Pannetier
  • PCP. Chesné
    P. Chesné
  • YHY. Heyman
    Y. Heyman
  • LRL. Renault
    L. Renault
  • BMB. Mandon-Pépin
    B. Mandon-Pépin
  • XVX. Vignon
    X. Vignon
  • JVJ.-L. Vilotte
    J.-L. Vilotte
  • CCC. Cotinot
    C. Cotinot
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Abstract
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 gonad-associated phenotype. Its invalidation in goat will help to better understand this complex syndrome.