title: Attempt to rescue sex-reversal by transgenic expression of the PISRT1 gene in XX PIS-/- goats.
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.
authors.affiliation: INRA, Biologie du Développement et Reproduction, Jouy en Josas, France.
authors.forename: L
authors.initials: L
authors.lastname: Boulanger
authors.forename: A
authors.initials: A
authors.lastname: Kocer
authors.forename: N
authors.initials: N
authors.lastname: Daniel
authors.forename: M
authors.initials: M
authors.lastname: Pannetier
authors.forename: P
authors.initials: P
authors.lastname: Chesné
authors.forename: Y
authors.initials: Y
authors.lastname: Heyman
authors.forename: L
authors.initials: L
authors.lastname: Renault
authors.forename: B
authors.initials: B
authors.lastname: Mandon-Pépin
authors.forename: P
authors.initials: P
authors.lastname: Chavatte-Palmer
authors.forename: X
authors.initials: X
authors.lastname: Vignon
authors.forename: J-L
authors.initials: JL
authors.lastname: Vilotte
authors.forename: C
authors.initials: C
authors.lastname: Cotinot
authors.forename: J-P
authors.initials: JP
authors.lastname: Renard
authors.forename: E
authors.initials: E
authors.lastname: Pailhoux