Highly Prolific Booroola Sheep Have a Mutation in the Intracellular Kinase Domain of Bone Morphogenetic Protein IB Receptor (ALK-6) That Is Expressed in Both Oocytes and Granulosa Cells

• Published in: Biology of reproduction Vol. 64; no. 4; pp. 1225 - 1235
• Main Authors: WILSON, Theresa, WU, Xi-Yang, MCNATTY, Kenneth P, MONTGOMERY, Grant W, JUENGEL, Jennifer L, ROSS, Ian K, LUMSDEN, Joanne M, LORD, Eric A, DODDS, Ken G, WALLING, Grant A, MCEWAN, John C, O'CONNELL, Anne R
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction 01-04-2001
• Subjects: Activin Receptors; ALK-6 protein; Amino Acid Sequence; Animals; Biological and medical sciences; BMPR-IB protein; bone morphogenetic protein receptors IB; Bone Morphogenetic Proteins - physiology; Cell Size; Chromosome Mapping; Conserved Sequence; DNA, Complementary - chemistry; FecB gene; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; Genotype; Granulosa Cells - chemistry; Humans; Male; Mammalian female genital system; Molecular Sequence Data; Morphology. Physiology; Oocytes - chemistry; Oocytes - cytology; Ovulation - genetics; Point Mutation; Polymorphism, Restriction Fragment Length; Protein Kinases - chemistry; Protein Kinases - genetics; Protein-Serine-Threonine Kinases - chemistry; Protein-Serine-Threonine Kinases - genetics; RNA, Messenger - analysis; Sequence Analysis, DNA; Sequence Homology; Sheep - genetics; Sheep - physiology; Signal Transduction; Vertebrates: reproduction; Genotype; Gene expression; Ovary; Vertebrata; Mammalia; Bone morphogenetic protein; Female genital system; Sheep; Artiodactyla; Granulosa; Mutation; Localization; Ovarian follicle; Ungulata; Oocyte; Biological receptor
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod64.4.1225

The Booroola fecundity gene ( FecB ) increases ovulation rate and litter size in sheep and is inherited as a single autosomal locus. The effect of FecB is additive for ovulation rate (increasing by about 1.6 corpora lutea per cycle for each copy) and has been mapped to sheep
chromosome 6q23–31, which is syntenic to human chromosome 4q21–25. Bone morphogenetic protein IB (BMP-IB) receptor (also known
as ALK-6), which binds members of the transforming growth factor-β (TGF-β) superfamily, is located in the region containing
the FecB locus. Booroola sheep have a mutation (Q249R) in the highly conserved intracellular kinase signaling domain of the BMP-IB
receptor. The mutation segregated with the FecB phenotype in the Booroola backcross and half-sib flocks of sheep with no recombinants. The mutation was not found in individuals
from a number of sheep breeds not derived from the Booroola strain. BMPR-IB was expressed in the ovary and in situ hybridization
revealed its specific location to the oocyte and the granulosa cell. Expression of mRNA encoding the BMP type II receptor
was widespread throughout the ovary. The mutation in BMPR-IB found in Booroola sheep is the second reported defect in a gene
from the TGF-β pathway affecting fertility in sheep following the recent discovery of mutations in the growth factor, GDF9b/BMP15.