Spontaneous mutagenesis is enhanced in Apex heterozygous mice

Jessica Huamani, C. Alex McMahan, Damon C. Herbert, Robert Reddick, John R. McCarrey, Mark I. MacInnes, David J. Chen, Christi A. Walter

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52 Scopus citations

Abstract

Germ line DNA directs the development of the next generation and, as such, is profoundly different from somatic cell DNA. Spermatogenic cells obtained from young adult lacI transgenic mice display a lower spontaneous mutant frequency and greater in vitro base excision repair activity than somatic cells and tissues obtained from the same mice. However, spermatogenic cells from old lacI mice display a 10-fold higher mutant frequency. This increased spontaneous mutant frequency occurs coincidentally with decreased in vitro base excision repair activity for germ cell and testicular extracts that in turn corresponds to a decreased abundance of AP endonuclease. To directly test whether a genetic diminution of AP endonuclease results in increased spontaneous mutant frequencies in spermatogenic cell types, AP endonuclease heterozygous (Apex +/-) knockout mice were crossed with lacI transgenic mice. Spontaneous mutant frequencies were significantly elevated (approximately twofold) for liver and spleen obtained from 3-month-old Apex+/- lacI+ mice compared to frequencies from Apex+/+ lacI + littermates and were additionally elevated for somatic tissues from 9-month-old mice. Spermatogenic cells from 9-month-old Apex+/- lacI+ mice were significantly elevated twofold compared to levels for 9-month-old Apex+/+ lacI+ control mice. These data indicate that diminution of AP endonuclease has a significant effect on spontaneous mutagenesis in somatic and germ line cells.

Original languageEnglish (US)
Pages (from-to)8145-8153
Number of pages9
JournalMolecular and cellular biology
Volume24
Issue number18
DOIs
StatePublished - Sep 1 2004

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Huamani, J., McMahan, C. A., Herbert, D. C., Reddick, R., McCarrey, J. R., MacInnes, M. I., Chen, D. J., & Walter, C. A. (2004). Spontaneous mutagenesis is enhanced in Apex heterozygous mice. Molecular and cellular biology, 24(18), 8145-8153. https://doi.org/10.1128/MCB.24.18.8145-8153.2004