title: Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Mérino ewes.
abstract: Ewes from the Booroola strain of Australian Mérino sheep are characterized by high ovulation rate and litter size. This phenotype is due to the action of the FecB(B) allele of a major gene named FecB, as determined by statistical analysis of phenotypic data. By genetic analysis of 31 informative half-sib families from heterozygous sires, we showed that the FecB locus is situated in the region of ovine chromosome 6 corresponding to the human chromosome 4q22-23 that contains the bone morphogenetic protein receptor IB (BMPR-IB) gene encoding a member of the transforming growth factor-beta (TGF-beta) receptor family. A nonconservative substitution (Q249R) in the BMPR-IB coding sequence was found to be associated fully with the hyperprolificacy phenotype of Booroola ewes. In vitro, ovarian granulosa cells from FecB(B)/FecB(B) ewes were less responsive than granulosa cells from FecB(+)/FecB(+) ewes to the inhibitory effect on steroidogenesis of GDF-5 and BMP-4, natural ligands of BMPR-IB. It is suggested that in FecB(B)/FecB(B) ewes, BMPR-IB would be inactivated partially, leading to an advanced differentiation of granulosa cells and an advanced maturation of ovulatory follicles.
authors.affiliation: Institut National de la Recherche Agronomique, Laboratoire de Génétique Cellulaire, BP, 27, 31326 Castanet-Tolosan, France. mulsant@toulouse.inra.fr
authors.forename: P
authors.initials: P
authors.lastname: Mulsant
authors.forename: F
authors.initials: F
authors.lastname: Lecerf
authors.forename: S
authors.initials: S
authors.lastname: Fabre
authors.forename: L
authors.initials: L
authors.lastname: Schibler
authors.forename: P
authors.initials: P
authors.lastname: Monget
authors.forename: I
authors.initials: I
authors.lastname: Lanneluc
authors.forename: C
authors.initials: C
authors.lastname: Pisselet
authors.forename: J
authors.initials: J
authors.lastname: Riquet
authors.forename: D
authors.initials: D
authors.lastname: Monniaux
authors.forename: I
authors.initials: I
authors.lastname: Callebaut
authors.forename: E
authors.initials: E
authors.lastname: Cribiu
authors.forename: J
authors.initials: J
authors.lastname: Thimonier
authors.forename: J
authors.initials: J
authors.lastname: Teyssier
authors.forename: L
authors.initials: L
authors.lastname: Bodin
authors.forename: Y
authors.initials: Y
authors.lastname: Cognié
authors.forename: N
authors.initials: N
authors.lastname: Chitour
authors.forename: J M
authors.initials: JM
authors.lastname: Elsen
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001315:Australia; D001483:Base Sequence; D055415:Bone Morphogenetic Protein 4; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D005260:Female; D005298:Fertility / Q000235:genetics; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D055428:Growth Differentiation Factor 5; D006133:Growth Substances / Q000494:pharmacology; D006579:Heterozygote; D006801:Humans; D008098:Litter Size / Q000235:genetics; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010060:Ovulation / Q000235:genetics*; D010641:Phenotype; D020161:Physical Chromosome Mapping; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017978:Receptors, Growth Factor; D016415:Sequence Alignment; D012756:Sheep / Q000235:genetics* / Q000502:physiology*
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5; D006133:Growth Substances; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D052004:Bone Morphogenetic Protein Receptors