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

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)127-134
Number of pages8
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume556
Issue number1-2
DOIs
StatePublished - Nov 22 2004
Externally publishedYes

Fingerprint

Apoptosis Inducing Factor
Mutation
Brain
Ataxia
Cell Count
DNA
Genes

Keywords

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

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

Cite this

Increased mutation in mice genetically predisposed to oxidative damage in the brain. / Stringer, James R.; Larson, Jon S.; Fischer, Jared; Stringer, Saundra L.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 556, No. 1-2, 22.11.2004, p. 127-134.

Research output: Contribution to journalArticle

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