The results of the present study demonstrate that an increase in the level of 8-oxodG in the cerebellum of BTBR T+tf/J mice may be largely related to the profound inhibition of the Ogg1 expression. In addition to Ogg1 down-regulation, an observed upregulation of Cdkn1a and Ccnd1 genes may contribute to an elevation of 8-oxodG in DNA in BTBR T+tf/J mice. OGG1 is a key enzyme preventing the accumulation of 8-oxodG in DNA through recognizing and removing 8-oxodG from DNA and initiating the highly conserved base excision repair pathway. Since OGG1 is the first enzyme in the base excision DNA repair pathway, the accurate DNA repair greatly depends on the ability of OGG1 to remove 8-oxodG. Ogg1 is highly expressed in the brain and has been shown to protect neurons against oxidative DNA damage during development and various pathologic conditions. A lack of Ogg1 in the brain resulted in multiple cellular and molecular events, including increased apoptosis and aberrant neuronal connectivity, key pathomorphological features of autism. Additionally, it is well-established that the accumulation of 8-oxodG in the genome caused by inhibition of OGG1 is a key event in the pathogenesis of several human pathologies, including cancer, neurodegeneration, Parkinson’s disease, and obesity and metabolic dysfunction. Several mechanisms may contribute to the inhibition of Ogg1 BAY-60-7550 expression in BTBR T+tf/J mice. Since the promoter region of the mouse Ogg1 gene contains a strong CpG island and because of an elevated genomic content of 5mC, a number of epigenetic mechanisms may be involved in Ogg1 gene silencing. However, the bisulfite sequencing analysis of the Ogg1 promoter region did not show differences in CpG methylation between the two mouse strains. It is possible that genespecific histone modifications at the Ogg1 promoter region could cause an inhibition of the Ogg1 expression in the cerebellum of BTBR T+tf/J mice; however, despite the fact that we did not observe alterations in the level of global histone modifications. There are other interconnected molecular mechanisms that could contribute to Ogg1 down-regulation. Specifically, it is well-established that TSC2 is a key regulator of the Ogg1 gene. Down-regulation of TSC2 or genetic deficiency of Tsc2 has been reported to cause a marked decrease of Ogg1 mRNA that was accompanied by the accumulation of 8-oxoG in DNA. The loss of TSC2 has been associated with various neuropsychological disorders. Importantly Reith et al. and Tsai et al. have reported that genetic Tsc2 or Tsc1 deficiency causes Purkinje cell degeneration and the development of autism-like phenotype. The results of the present study demonstrating only moderate changes in the level of TSC2 protein in the cerebellum of BTBR T+tf/J mice indicate that this mechanism may not be a main cause of the Ogg1 inhibition. Finally, inhibition of Ogg1 may be caused by genetic variations. A computational analysis of the Ogg1 gene, using the GeneNetwork database, revealed substantial differences in single nucleotide polymorphisms located in coding and non-coding regions of Ogg1 between BTBR T+tf/J and C57BL/6J mice that may explain a reduced gene expression in BTBR T+tf/J mice.