Epidemiological and imaging studies are not able to address causality or the molecular underpinnings of the disease. Animal models that resemble core human autistic symptoms may substantially overcome the limitations of human studies and have the flexibility to provide important additional clues regarding the etiology and molecular pathogenesis of autism. Several mouse models have been developed to simulate autism symptoms in humans. Among all mouse models, the inbred BTBR T+tf/J mice is one of the most relevant and commonly used animal models to study autism because they exhibit an autism-like behavioral phenotype. In addition to behavioral similarities, multiple studies have shown that BTBR T+tf/J mice share many similarities in neuroanatomical and physiological features found in individuals with autism. Escalating evidence suggests that oxidative stress and aberrations in the cellular epigenome, especially aberrant DNA methylation, are key molecular features of autistic phenotype that are linked to alterations in glutathione metabolism and folate-dependent trans-methylation and trans-sulfuration pathways. While alterations causing these pathological signs are of great importance, little is known about the underlying mechanisms responsible for their persistence in the pathophysiology of autism. Based on these considerations, the goal of this study was to evaluate key molecular alterations postulated to play a role in autism and their role in the pathophysiology of autism using inbred BTBR T+tf/J mice, a strain that exhibits an autism-like behavioral phenotype, including deficits in reciprocal social interactions and social approach, and high levels of repetitive self-grooming behavior in contrast to C57BL/6J mice, a mouse strain ABT-199 characterized by a high sociability and low grooming behavior. Autism is a complex disorder that is thought to be the consequence of multiple interdependent events during development. The transcriptomic analysis of the cerebellum of BTBR T+tf/J mice demonstrates a profoundly dysregulated expression of cell cycle/stress-related genes, mainly p53 apoptotic signaling, DNA damage and repair, and chromatin modifying genes. These findings are in good agreement with previous reports that have convincingly established a dysregulation of these molecular pathways in autistic brain. Oxidative stressinduced damage to DNA and aberrant DNA methylation are considered as key events, since both of them, in addition to genetic factors, may contribute to the heritability of autism. In this study, we demonstrate that DNA isolated from the cerebellum of BTBR T+tf/J mice and post-mortem cerebellum of individuals with autism, is characterized by an increased levels of 8-oxodeoxyguanosine, 5- methylcytosine, and 5-hydroxymethylcytosine. 8-oxodG is one of the prevalent and most studied oxidative DNA lesion and oxidative stress marker. Several comprehensive studies have established the important role of the altered cellular redox status in the pathophysiology of autism. The majority of those studies have largely focused on the potential causes of the oxidative stress induction, mainly on the glutathione redox imbalance and mitochondrial dysfunction.