Project description:Fmr1 mutation results in autistic behaviors and the FMR1 KO mice model is one of the popular methods to study autism spectrum disorders. In this dataset, we include the expression data obtained from astrocytes isolated from cortex of control and FMR1-KO mice.
Project description:In this dataset we include the expression data obtained by dissected prefrontal cortical tissue from sprague-dawley rats exposed to saline or valproic acid on gestation day 12.5 in utero. This data was used to obtain prefrontal cortical genes to determine sex differences in a model of autism spectrum disorder.
Project description:The molecular pathogenesis of autism is complex and involves numerous genomic, epigenomic, proteomic, metabolic, and physiological alterations. Elucidating and understanding the molecular processes underlying the pathogenesis of autism is critical for effective clinical management and prevention of this disorder. The goal of this study is to investigate key molecular alterations postulated to play a role in autism and their role in the pathophysiology of autism. In this study we demonstrate that DNA isolated from the cerebellum of BTBR T+tf/J mice, a relevant mouse model of autism, and from human post-mortem cerebellum of individuals with autism, are both characterized by an increased levels of 8-oxo-7-hydrodeoxyguanosine (8-oxodG), 5-methylcytosine (5mC), and 5-hydroxymethylcytosine (5hmC). The increase in 8-oxodG and 5mC content was associated with a markedly reduced expression of the 8-oxoguanine DNA-glycosylase 1 (Ogg1) and increased expression of de novo DNA methyltransferases 3a and 3b (Dnmt3a and Dnmt3b). Interestingly, a rise in the level of 5hmC occurred without changes in the expression of ten-eleven translocation expression 1 (Tet1) and Tet2 genes, but significantly correlated with the presence of 8-oxodG in DNA. This finding and similar elevation in 8-oxodG in cerebellum of individuals with autism and in the BTBR T+tf/J mouse model warrant future large-scale studies to specifically address the role of genetic alterations in OGG1 in pathogenesis of autism. Gene expression profiles in the cerebellum of 8 weeks old BTBR T+tf/J mice that exhibit an autism-like behavioral phenotype and control C57BL/6J mice were examined using high-throughput Agilent whole genome 8x60K mouse microarrays.
Project description:Type III adenylyl cyclase (AC3, ADCY3) is predominantly enriched in neuronal primary cilia throughout the central nervous system (CNS). Genome-wide association studies in humans have associated ADCY3 with major depressive disorder and autistic spectrum disorder, both of which exhibit sexual dimorphism. To date, it is unclear how AC3 affects protein phosphorylation and signal networks in central neurons, and what causes the sexual dimorphism of autism. We employed a mass spectrometry (MS)-based phosphoproteomic approach to quantitatively profile differences in phosphorylation between inducible AC3 knockout (KO) and wild type (WT), male and female mice. In total, we identified 4655 phosphopeptides from 1756 proteins, among which 565 phosphopeptides from 322 proteins were repetitively detected in all samples. Comparison of AC3 KO and WT datasets revealed that phosphopeptides with motifs matching proline-directed kinases’ recognition sites had a lower abundance in the KO dataset than in WTs. We detected 14 phosphopeptides restricted to WT dataset (i.e., from Spast and Ppp1r14a) and 35 exclusively in KOs (i.e., from Sptan1, Arhgap20, Arhgap44, and Pde1b). Moreover, 95 phosphopeptides were identified only in female dataset and 26 only in males. Label-free MS spectrum quantification using Skyline further identified phosphopeptides that had high expression abundance in each sample group. In total, over 200 modifications were gender-biased and had increased expression in females relative to males. 29% gender-biased phosphopeptides were from autism-associated proteins, including Dlg1, Dlg4, Dlgap2, Syn1, Syngap1, Ctnna1, Ctnnd1, Ctnnd2, Pkp4, and Arvcf. These autism proteins were well-connected in protein-protein interaction network that centered around Dlg4. This study provided the first phosphoproteomics evidence, suggesting that gender-biased post-translational phosphorylation may be implicated in the sexual dimorphism of autism.