Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice

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Aneuploidy, the most common chromosomal abnormality at birth and the main ascertained cause of pregnancy loss in humans, originates primarily from chromosome segregation errors during oogenesis. Here we report that heterozygosity for a mutation in the mitotic checkpoint kinase gene, Bub1, induces aneuploidy in female germ cells of mice, and that the effect increases with advancing maternal age. Analysis of Bub1 heterozygous oocytes showed that aneuploidy occurred primarily during the first meiotic division and involved premature sister chromatid separation. Furthermore, aneuploidy was inherited in zygotes and resulted in the loss of embryos after implantation. The incidence of aneuploidy in zygotes ... continued below

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Leland, Shawn; Nagarajan, Prabakaran; Polyzos, Aris; Thomas, Sharon; Samaan, George; Donnell, Robert et al. June 24, 2009.

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Aneuploidy, the most common chromosomal abnormality at birth and the main ascertained cause of pregnancy loss in humans, originates primarily from chromosome segregation errors during oogenesis. Here we report that heterozygosity for a mutation in the mitotic checkpoint kinase gene, Bub1, induces aneuploidy in female germ cells of mice, and that the effect increases with advancing maternal age. Analysis of Bub1 heterozygous oocytes showed that aneuploidy occurred primarily during the first meiotic division and involved premature sister chromatid separation. Furthermore, aneuploidy was inherited in zygotes and resulted in the loss of embryos after implantation. The incidence of aneuploidy in zygotes was sufficient to explain the reduced litter size in matings with Bub1 heterozygous females. No effects were seen in germ cells from heterozygous males. These findings show that Bub1 dysfunction is linked to inherited aneuploidy in female germ cells and may contribute to the maternal age-related increase in aneuploidy and pregnancy loss.

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  • Journal Name: Proceedings of the National Academy of Sciences USA; Journal Volume: 106; Journal Issue: 31; Related Information: Journal Publication Date: August 4, 2009

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  • Report No.: LBNL-2713E
  • Grant Number: DE-AC02-05CH11231
  • Office of Scientific & Technical Information Report Number: 974252
  • Archival Resource Key: ark:/67531/metadc928068

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  • June 24, 2009

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  • Nov. 13, 2016, 7:26 p.m.

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  • Nov. 18, 2016, 3:48 p.m.

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Leland, Shawn; Nagarajan, Prabakaran; Polyzos, Aris; Thomas, Sharon; Samaan, George; Donnell, Robert et al. Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice, article, June 24, 2009; Berkeley, California. (digital.library.unt.edu/ark:/67531/metadc928068/: accessed October 22, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.