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

Research output: Contribution to journalArticle

49 Citations (Scopus)

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 2004

Fingerprint

Mutagenesis
DNA-(Apurinic or Apyrimidinic Site) Lyase
Germ Cells
DNA Repair
Transgenic Mice
DNA
Cell Extracts
Knockout Mice
Young Adult
Spleen
Liver
In Vitro Techniques

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Huamani, J., McMahan, C. A., Herbert, D. C., Reddick, R., McCarrey, J. R., MacInnes, M. I., ... 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

Spontaneous mutagenesis is enhanced in Apex heterozygous mice. / Huamani, Jessica; McMahan, C. Alex; Herbert, Damon C.; Reddick, Robert; McCarrey, John R.; MacInnes, Mark I.; Chen, David J.; Walter, Christi A.

In: Molecular and Cellular Biology, Vol. 24, No. 18, 09.2004, p. 8145-8153.

Research output: Contribution to journalArticle

Huamani, J, McMahan, CA, Herbert, DC, Reddick, R, McCarrey, JR, MacInnes, MI, Chen, DJ & Walter, CA 2004, 'Spontaneous mutagenesis is enhanced in Apex heterozygous mice', Molecular and Cellular Biology, vol. 24, no. 18, pp. 8145-8153. https://doi.org/10.1128/MCB.24.18.8145-8153.2004
Huamani J, McMahan CA, Herbert DC, Reddick R, McCarrey JR, MacInnes MI et al. Spontaneous mutagenesis is enhanced in Apex heterozygous mice. Molecular and Cellular Biology. 2004 Sep;24(18):8145-8153. https://doi.org/10.1128/MCB.24.18.8145-8153.2004
Huamani, Jessica ; McMahan, C. Alex ; Herbert, Damon C. ; Reddick, Robert ; McCarrey, John R. ; MacInnes, Mark I. ; Chen, David J. ; Walter, Christi A. / Spontaneous mutagenesis is enhanced in Apex heterozygous mice. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 18. pp. 8145-8153.
@article{5cfff80bdaff45a09b56316ee9e296c4,
title = "Spontaneous mutagenesis is enhanced in Apex heterozygous mice",
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.",
author = "Jessica Huamani and McMahan, {C. Alex} and Herbert, {Damon C.} and Robert Reddick and McCarrey, {John R.} and MacInnes, {Mark I.} and Chen, {David J.} and Walter, {Christi A.}",
year = "2004",
month = "9",
doi = "10.1128/MCB.24.18.8145-8153.2004",
language = "English (US)",
volume = "24",
pages = "8145--8153",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "18",

}

TY - JOUR

T1 - Spontaneous mutagenesis is enhanced in Apex heterozygous mice

AU - Huamani, Jessica

AU - McMahan, C. Alex

AU - Herbert, Damon C.

AU - Reddick, Robert

AU - McCarrey, John R.

AU - MacInnes, Mark I.

AU - Chen, David J.

AU - Walter, Christi A.

PY - 2004/9

Y1 - 2004/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=4444294284&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4444294284&partnerID=8YFLogxK

U2 - 10.1128/MCB.24.18.8145-8153.2004

DO - 10.1128/MCB.24.18.8145-8153.2004

M3 - Article

VL - 24

SP - 8145

EP - 8153

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 18

ER -