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FOXL2 is a female sex-determining gene in the goat

Abstract : For decades, a strange mutation traveled goat herd that make sometimes appear intersex male goats with XX genotype. The associated mutation, even unknown, was over selected because of absence of horns in heterozygous individuals. The origin of sex reversal in XX goats homozygous for the polled intersex syndrome (PIS) mutation was unclear because of the complexity of the mutation that affects the transcription of both FOXL2 and several long non coding RNAs (lncRNAs). Accumulating evidence suggested that FOXL2 could be the sole gene of the PIS locus responsible for XX sex reversal, the lncRNAs being involved in transcriptional regulation of FOXL2. Using zinc finger nuclease (ZFN) directed mutagenesis, we tried to knock out the FOXL2 gene in a normal genotype. In order to help for the selection of ZFN expressing embryos, we constructed a biZFN-EGFP marker plasmid that expresses both part of the ZFN and an EGFP fluorescent protein at the same time to select the embryos under fluorescent microscope. After transfer of ZFN microinjected embryos, we generated several fetuses, of which one XX individual bears biallelic mutations of FOXL2. Our analysis demonstrates that FOXL2 loss of function dissociated from loss of lncRNA expression is sufficient to cause an XX female to male sex reversal in the goat model and, as in the mouse, agenesis of eyelids. Both developmental defects were reproduced in two newborn animals cloned from the XX FOXL2-/- fibroblasts. These results therefore identify FOXL2 as a bona fide female sex-determining gene in the goat. They also highlight a stage-dependent role of FOXL2 in the ovary, different between goats and mice, being important for fetal development in the former but for postnatal maintenance in the latter. To improve this goat model we will target other genes implicated in male or female gonadal development way with the recent TALEN or CRISPR/Cas9 tools that seem to show much higher level of efficiency in this species.
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Submitted on : Wednesday, June 3, 2020 - 12:36:09 AM
Last modification on : Wednesday, June 1, 2022 - 12:52:02 PM


  • HAL Id : hal-02741098, version 1
  • PRODINRA : 277578



Laurent Boulanger, Maëlle Pannetier, Laurence Gall Pouget Gall, Aurélie Allais-Bonnet, Maeva M. El Zaiat, et al.. FOXL2 is a female sex-determining gene in the goat. Opening Conference "COST Action BM1308. Sharing Advances on Large Animal Models", European Cooperation in Science and Technology (COST). BEL., Dec 2014, Munich, Germany. ⟨hal-02741098⟩



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