Increased mutation in mice genetically predisposed to oxidative damage in the brain

James R. Stringer; Jon S. Larson; Jared M. Fischer; Saundra L. Stringer

doi:10.1016/j.mrfmmm.2004.07.010

Increased mutation in mice genetically predisposed to oxidative damage in the brain

James R. Stringer, Jon S. Larson, Jared M. Fischer, Saundra L. Stringer

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Harlequin (Hq) mice develop ataxia due to an X-linked recessive mutation in the gene encoding apoptosis-inducing factor (Aif). Brain cells in Hq mice contain the modified base 8-hydroxydeoxyguanosine (8-OHdG), suggesting that the defect in Aif causes increased DNA oxidation in these cells. Because oxidative damage is mutagenic, Hq mice might suffer increased mutation in the brain. To examine this possibility, mutation in the brain was assessed using the Tg(βA-G11PLAP) mouse model, which allows mutant cells to be visualized in tissue sections in situ. Hq mice exhibited more and larger patches of PLAP positive tissue in the brain. PLAP+ cells were observed in all areas of the brain. No increase in the number of PLAP+ cells was seen in three other tissues, suggesting that the effect of Aif deficiency on mutation was specific to brain.

Original language	English (US)
Pages (from-to)	127-134
Number of pages	8
Journal	Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume	556
Issue number	1-2
DOIs	https://doi.org/10.1016/j.mrfmmm.2004.07.010
State	Published - Nov 22 2004
Externally published	Yes

Keywords

Apoptosis-inducing factor
Brain
In situ
Mononucleotide repeat
Mutation
Oxidative damage

ASJC Scopus subject areas

Molecular Biology
Genetics
Health, Toxicology and Mutagenesis

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10.1016/j.mrfmmm.2004.07.010

Cite this

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title = "Increased mutation in mice genetically predisposed to oxidative damage in the brain",

abstract = "Harlequin (Hq) mice develop ataxia due to an X-linked recessive mutation in the gene encoding apoptosis-inducing factor (Aif). Brain cells in Hq mice contain the modified base 8-hydroxydeoxyguanosine (8-OHdG), suggesting that the defect in Aif causes increased DNA oxidation in these cells. Because oxidative damage is mutagenic, Hq mice might suffer increased mutation in the brain. To examine this possibility, mutation in the brain was assessed using the Tg(βA-G11PLAP) mouse model, which allows mutant cells to be visualized in tissue sections in situ. Hq mice exhibited more and larger patches of PLAP positive tissue in the brain. PLAP+ cells were observed in all areas of the brain. No increase in the number of PLAP+ cells was seen in three other tissues, suggesting that the effect of Aif deficiency on mutation was specific to brain.",

keywords = "Apoptosis-inducing factor, Brain, In situ, Mononucleotide repeat, Mutation, Oxidative damage",

author = "Stringer, {James R.} and Larson, {Jon S.} and Fischer, {Jared M.} and Stringer, {Saundra L.}",

note = "Funding Information: This work was supported by grant P42 ES04908 from the National Institute of Environmental Health Sciences (NIEHS). J.S. Larson was supported by NIEHS Division of Extramural Research and Training Grant, T32 ES07250. We thank Peter J. Stambrook, Thomas Doetschman, Moying Yin and Angel Whitaker and the Mouse Models of Human Cancers Consortium for help with support and maintenance of mouse colonies. We thank of Carolyn Tindal, Hillary A. Stringer and Adam Lenz for technical assistance.",

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doi = "10.1016/j.mrfmmm.2004.07.010",

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AU - Stringer, James R.

AU - Larson, Jon S.

AU - Fischer, Jared M.

AU - Stringer, Saundra L.

N1 - Funding Information: This work was supported by grant P42 ES04908 from the National Institute of Environmental Health Sciences (NIEHS). J.S. Larson was supported by NIEHS Division of Extramural Research and Training Grant, T32 ES07250. We thank Peter J. Stambrook, Thomas Doetschman, Moying Yin and Angel Whitaker and the Mouse Models of Human Cancers Consortium for help with support and maintenance of mouse colonies. We thank of Carolyn Tindal, Hillary A. Stringer and Adam Lenz for technical assistance.

PY - 2004/11/22

Y1 - 2004/11/22

N2 - Harlequin (Hq) mice develop ataxia due to an X-linked recessive mutation in the gene encoding apoptosis-inducing factor (Aif). Brain cells in Hq mice contain the modified base 8-hydroxydeoxyguanosine (8-OHdG), suggesting that the defect in Aif causes increased DNA oxidation in these cells. Because oxidative damage is mutagenic, Hq mice might suffer increased mutation in the brain. To examine this possibility, mutation in the brain was assessed using the Tg(βA-G11PLAP) mouse model, which allows mutant cells to be visualized in tissue sections in situ. Hq mice exhibited more and larger patches of PLAP positive tissue in the brain. PLAP+ cells were observed in all areas of the brain. No increase in the number of PLAP+ cells was seen in three other tissues, suggesting that the effect of Aif deficiency on mutation was specific to brain.

AB - Harlequin (Hq) mice develop ataxia due to an X-linked recessive mutation in the gene encoding apoptosis-inducing factor (Aif). Brain cells in Hq mice contain the modified base 8-hydroxydeoxyguanosine (8-OHdG), suggesting that the defect in Aif causes increased DNA oxidation in these cells. Because oxidative damage is mutagenic, Hq mice might suffer increased mutation in the brain. To examine this possibility, mutation in the brain was assessed using the Tg(βA-G11PLAP) mouse model, which allows mutant cells to be visualized in tissue sections in situ. Hq mice exhibited more and larger patches of PLAP positive tissue in the brain. PLAP+ cells were observed in all areas of the brain. No increase in the number of PLAP+ cells was seen in three other tissues, suggesting that the effect of Aif deficiency on mutation was specific to brain.

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Increased mutation in mice genetically predisposed to oxidative damage in the brain

Abstract

Keywords

ASJC Scopus subject areas

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