Highly prolific Booroola sheep have a mutation in the intracellular kinasedomain of bone morphogenetic protein IB receptor (ALK-6) that is expressedin both oocytes and granulosa cells

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 c ycle 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 transformin g growth factor-beta (TGF-beta) superfamily, is located in the region conta ining 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 i n individuals from a number of sheep breeds not derived from the Booroola s train. BMPR-IB was expressed in the ovary and in situ hybridization reveale d 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 de fect in a gene from the TGF-beta pathway affecting fertility in sheep follo wing the recent discovery of mutations in the growth factor, GDF96/BMP15.