| First Author | Kong SW | Year | 2014 |
| Journal | Mol Autism | Volume | 5 |
| Issue | 1 | Pages | 16 |
| PubMed ID | 24564913 | Mgi Jnum | J:355930 |
| Mgi Id | MGI:7762022 | Doi | 10.1186/2040-2392-5-16 |
| Citation | Kong SW, et al. (2014) Divergent dysregulation of gene expression in murine models of fragile X syndrome and tuberous sclerosis. Mol Autism 5(1):16 |
| abstractText | BACKGROUND: Fragile X syndrome and tuberous sclerosis are genetic syndromes that both have a high rate of comorbidity with autism spectrum disorder (ASD). Several lines of evidence suggest that these two monogenic disorders may converge at a molecular level through the dysfunction of activity-dependent synaptic plasticity. METHODS: To explore the characteristics of transcriptomic changes in these monogenic disorders, we profiled genome-wide gene expression levels in cerebellum and blood from murine models of fragile X syndrome and tuberous sclerosis. RESULTS: Differentially expressed genes and enriched pathways were distinct for the two murine models examined, with the exception of immune response-related pathways. In the cerebellum of the Fmr1 knockout (Fmr1-KO) model, the neuroactive ligand receptor interaction pathway and gene sets associated with synaptic plasticity such as long-term potentiation, gap junction, and axon guidance were the most significantly perturbed pathways. The phosphatidylinositol signaling pathway was significantly dysregulated in both cerebellum and blood of Fmr1-KO mice. In Tsc2 heterozygous (+/-) mice, immune system-related pathways, genes encoding ribosomal proteins, and glycolipid metabolism pathways were significantly changed in both tissues. CONCLUSIONS: Our data suggest that distinct molecular pathways may be involved in ASD with known but different genetic causes and that blood gene expression profiles of Fmr1-KO and Tsc2+/- mice mirror some, but not all, of the perturbed molecular pathways in the brain. |
