Increased mutation in mice genetically predisposed to oxidative damage in the brain.
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(betaA-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.
Stringer
James R
JR
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Cincinnati, OH 45267, USA.
Larson
Jon S
JS
Fischer
Jared M
JM
Stringer
Saundra L
SL
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D017931:DNA Primers; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D018384:Oxidative Stress; D010920:Placenta / Q000201:enzymology
D017931:DNA Primers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000469:Alkaline Phosphatase; D003849:Deoxyguanosine