期刊
REPRODUCTION
卷 138, 期 6, 页码 921-933出版社
BIOSCIENTIFICA LTD
DOI: 10.1530/REP-09-0193
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资金
- Medical Research Council [U.1276.00.002.00007.01]
- Rural Environment Research and Analysis Department of the Scottish Government
- BBSRC through the Roslin Institute ISPG
- BBSRC [BBS/E/D/05191132] Funding Source: UKRI
- MRC [MC_U127685843] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/E/D/05191132] Funding Source: researchfish
- Medical Research Council [MC_U127685843] Funding Source: researchfish
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. Reproduction (2009) 138 921-933
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