MTH1 and OGG1 maintain a low level of 8-oxoguanine in Alzheimer's brain, and prevent the progression of Alzheimer's pathogenesis. Mus musculus

To investigate the role of 8-oxo-7, 8-dihydroguanine (8-oxoguanine) accumulation in DNA or nucleotide pools during the development of AD pathology, we introduced a Mth1/Ogg1-double deficiency into homozygous triple-transgenic AD model (3xTg-AD-H) mice. Mth1 encodes 8-oxo-7, 8-dihydro-2'-deoxyguanosine-5'-triphosphatase (8-oxo-dGTPase) and Ogg1 encodes 8-oxoguanine DNA glycosylase 1. One-way eBays ANOVA of microarray data from hippocampi revealed that the gene expression profiles are most significantly altered in the hippocampi of 3xTg-AD-H with Mth1/Ogg1-double deficient (ADH/TO-DKH) mice compared to non-Tg control (NT) mice. Comparative analysis between 3xTg-AD-H (ADH/WT) and ADH/TO-DKH mice showed that the expression of genes involved in neuroprotection are significantly altered. Among them, expression of the AD-related genes including Ttr, Enpp2, Kcnj13 and Kl was significantly downregulated in ADH/TO-DKH mice. Overall design: Non-transgenic control (NT) , homozygous 3xTg-AD mice harboring homozygous APPSwe and tauP301L transgenes with a homozygous Psen1M146V mutation (ADH/WT), and homozygous 3xTg-AD mice with MTH1/OGG1-double deficiency (ADH/TO-DKH), were used in this study (5-month-old, male, n=3 for each group). RNA samples prepared from hippocampi were subjected to microarray analysis using the Affymetrix Mouse Gene 1.0 ST platform.