title: A novel mutation in the bone morphogenetic protein 15 gene causing defective protein secretion is associated with both increased ovulation rate and sterility in Lacaune sheep.
abstract: Genetic mutations with major effects on ovulation rate and litter size in sheep were recently identified in three genes belonging to the TGFbeta superfamily pathway: the bone morphogenetic protein 15 (BMP15, also known as GDF9b), growth differentiation factor 9 (GDF9), and BMP receptor type IB (also known as activin-like kinase 6). Homozygous BMP15 or GDF9 mutations raise female sterility due to a failure of normal ovarian follicle development, whereas heterozygous animals for BMP15 or GDF9 as well as heterozygous and homozygous animals for BMP receptor type IB show increased ovulation rates. In the present work, a new naturally occurring mutation in the BMP15 gene in the high prolific Lacaune sheep breed is described. The identified variant is a C53Y missense nonconservative substitution leading to the aminoacidic change of a cysteine with a tyrosine in the mature peptide of the protein. As for other mutations found in the same gene, this is associated with an increased ovulation rate and sterility in heterozygous and homozygous animals, respectively. Further in vitro studies showed that the C53Y mutation was responsible for the impairment of the maturation process of the BMP15 protein, resulting in a defective secretion of both the precursor and mature peptide. Overall, our findings confirm the essential role of the BMP15 factor in the ovarian folliculogenesis and control of ovulation rate in sheep.
authors.affiliation: Institut National de la Recherche Agronomique, UR631, tation d'Amélioration Génétique des Animaux, BP 52627, 31326 Castanet-Tolosan, France. loys.bodin@toulouse.inra.fr
authors.forename: Loys
authors.initials: L
authors.lastname: Bodin
authors.forename: Elisa
authors.initials: E
authors.lastname: Di Pasquale
authors.forename: Stéphane
authors.initials: S
authors.lastname: Fabre
authors.forename: Martine
authors.initials: M
authors.lastname: Bontoux
authors.forename: Philippe
authors.initials: P
authors.lastname: Monget
authors.forename: Luca
authors.initials: L
authors.lastname: Persani
authors.forename: Philippe
authors.initials: P
authors.lastname: Mulsant
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D016384:Consensus Sequence; D005260:Female; D055429:Growth Differentiation Factor 9; D006579:Heterozygote; D006720:Homozygote; D007246:Infertility / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D006080:Ovarian Follicle / Q000473:pathology / Q000503:physiopathology; D010060:Ovulation / Q000502:physiology*; D017354:Point Mutation; D012756:Sheep / Q000235:genetics*; D012757:Sheep Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
chemical_list: D019485:Bone Morphogenetic Proteins; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins