Positional cloning of the PIS mutation in goats and its impact on understanding mammalian sex-differentiation

Eric Pailhoux; Bernard Vigier; Laurent Schibler; Edmond P. Cribiu; Corinne Cotinot; Daniel Vaiman

doi:doi:10.1051/gse:2004025

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Volume 37 / No Suppl. 1 (2005)

Genet. Sel. Evol., 37 Suppl. 1 (2005) S55-S64

Abstract

Free Access

Issue		Genet. Sel. Evol. Volume 37, Number Suppl. 1, 2005 International Workshop on Major Genes and QTL in Sheep and Goats


Page(s)		S55 - S64
DOI		https://doi.org/10.1051/gse:2004025

Genet. Sel. Evol. 37 (2005) S55-S64
DOI: 10.1051/gse:2004025

Positional cloning of the PIS mutation in goats and its impact on understanding mammalian sex-differentiation

Eric Pailhoux^a, Bernard Vigier^a, Laurent Schibler^b, Edmond P. Cribiu^b, Corinne Cotinot^a and Daniel Vaiman^c

^a Laboratoire de biologie du développement et reproduction, Institut national de la recherche agronomique, 78352 Jouy-en-Josas Cedex, France
^b Laboratoire de génétique biochimique et cytogénétique, Institut national de la recherche agronomique, 78352 Jouy-en-Josas Cedex, France
^c Laboratoire de génétique et épigénétique des pathologies placentaires, INSERM-U361, Pavillon Baudelocque, 123 Bd Port-Royal, 75014 Paris, France

(Accepted: 7 May 2004)

Abstract -
In goats, the PIS (polled intersex syndrome) mutation is responsible for both the absence of horns in males and females and sex-reversal affecting exclusively XX individuals. The mode of inheritance is dominant for the polled trait and recessive for sex-reversal. In XX PIS ^-/- mutants, the expression of testis-specific genes is observed very precociously during gonad development. Nevertheless, a delay of 4-5 days is observed in comparison with normal testis differentiation in XY males. By positional cloning, we demonstrate that the PIS mutation is an 11.7-kb regulatory-deletion affecting the expression of two genes, PISRT1 and FOXL2 which could act synergistically to promote ovarian differentiation. The transcriptional extinction of these two genes leads, very early, to testis-formation in XX homozygous PIS ^-/- mutants. According to their expression profiles and bibliographic data, we propose that FOXL2 may be an ovary-differentiating gene, and the non-coding RNA PISRT1, an anti-testis factor repressing SOX9, a key regulator of testis differentiation. Under this hypothesis, SRY, the testis-determining factor would inhibit these two genes in the gonads of XY males, to ensure testis differentiation.

Key words: PIS mutation / goat / gonad differentiation / XX sex-reversal / ovary development

Correspondence and reprints: pailhoux@jouy.inra.fr

© INRA, EDP Sciences 2004