Genetic variance modifies apoptosis susceptibility in mature oocytes via alterations in DNA repair capacity and mitochondrial ultrastructure

G. I. Perez, B. M. Acton, A. Jurisicova, G. A. Perkins, A. White, J. Brown, A. M. Trbovich, M. R. Kim, R. Fissore, J. Xu, A. Ahmady, S. G. D'Estaing, H. Li, W. Kagawa, H. Kurumizaka, S. Yokoyama, H. Okada, T. W. Mak, M. H. Ellisman, R. F. CasperJ. L. Tilly*

*この研究の対応する著者

研究成果: Article査読

47 被引用数 (Scopus)

抄録

Although the identification of specific genes that regulate apoptosis has been a topic of intense study, little is known of the role that background genetic variance plays in modulating cell death. Using germ cells from inbred mouse strains, we found that apoptosis in mature (metaphase II) oocytes is affected by genetic background through at least two different mechanisms. The first, manifested in AKR/J mice, results in genomic instability. This is reflected by numerous DNA double-strand breaks in freshly isolated oocytes, causing a high apoptosis susceptibility and impaired embryonic development following fertilization. Microinjection of Rad51 reduces DNA damage, suppresses apoptosis and improves embryonic development. The second, manifested in FVB mice, results in dramatic dimorphisms in mitochondrial ultrastructure. This is correlated with cytochrome c release and a high apoptosis susceptibility, the latter of which is suppressed by pyruvate treatment, Smac/DIABLO deficiency, or microinjection of 'normal' mitochondria. Therefore, background genetic variance can profoundly affect apoptosis in female germ cells by disrupting both genomic DNA and mitochondrial integrity.

本文言語English
ページ(範囲)524-533
ページ数10
ジャーナルCell Death and Differentiation
14
3
DOI
出版ステータスPublished - 2007 3月
外部発表はい

ASJC Scopus subject areas

  • 細胞生物学

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