This Article Full Text Full Text (PDF) Supplementary Data All Versions of this Article: 138/6/921    most recent REP-09-0193v1 Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Nicol, L. Articles by McNeilly, A. S PubMed PubMed Citation Articles by Nicol, L. Articles by McNeilly, A. S

Homozygosity for a single base-pair mutation in the oocyte-specific GDF9 gene results in sterility in Thoka sheep

MRC Human Reproductive Sciences Unit, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK¹ The Roslin Institute and R(D)SVS, Roslin BioCentre, University of Edinburgh, Midlothian EH25 9PS, UK² Department of Genetics and Biotechnology, Faculty of Agricultural Sciences, Aarhus University, DK-8830 Tjele, Denmark and³ The Macaulay Institute, Craigiebuckler, Aberdeen AB15 8QH, UK

Correspondence should be addressed to L Nicol; Email: l.nicol{at}hrsu.mrc.ac.uk

The control of fecundity is critical in determining mammalian offspring survival. It is regulated principally by the ovulation rate, so that primates and large farm species commonly have a single offspring. Previously, several mutations have been identified in sheep which increase the naturally low ovulation rate; although in some cases homozygous ewes are infertile. In the present study we present a detailed characterization of a novel mutation in growth differentiation factor 9 (GDF9), found in Icelandic Thoka sheep. This mutation is a single base change (A1279C) resulting in a nonconservative amino acid change (S109R) in the C-terminus of the mature GDF9 protein, which is normally expressed in oocytes at all stages of development. Genotyping all animals for which reproductive records were available confirmed this mutation to be associated with increased fecundity in heterozygous ewes and infertility in homozygotes. Analysis of homozygote ovarian morphology and a number of genes normally activated in growing follicles showed that GDF9 was not involved in oocyte activation, but in subsequent development of the follicle. This study highlights the importance of oocyte factors in regulating fertility and provides new information for structural analysis and investigation of the potentially important sites of dimerization or translational modifications required to produce biologically active GDF9. It also provides the basis for the utilization of these animals to enhance sheep production.