Prithvi Mohan
Prithvi Mohan
Prithvi Mohan
Helios Scholar
School: University of Arizona
Hometown: Phoenix, Arizona
Mentor: Vinodh Narayanan, M.D.
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Molecular characterization of the mTOR pathway in the MECP2 A140V mouse model of Rett Syndrom

Rett Syndrome (RTT) is a severe, X-linked neurological disorder that affects one in 10,000 female live births. Children with RTT experience developmental regression, loss of speech, breathing and gait abnormalities, and repetitive stereotype hand movements. The pathology of RTT has shown decreased neuronal size with increased cell packing, and decreased length and complexity of dendrites. MECP2 (methyl CpG binding protein 2 gene), which is a transcriptional modulator, has been implicated as the RTT gene. The mTOR-signaling pathway is considered vitally for cell size regulation, including neuronal size. Studies have indicated a general dysfunction of the Akt/mTOR pathway in Rett syndrome models, highlighting an essential role of MeCP2 in the regulation of mTOR pathway. However, the mechanism by which the MECP2 mutation causes the aforementioned RTT neuronal pathology by affecting the mTOR pathway is still unknown. To explore this question, the MECP2 A140V mouse model was used, and brain samples were harvested. Lysates were prepared from the samples, and western blots, ELISA assays, and mRNA expression assays were performed on the isolated protein and RNA.  We observed down-regulation specific to the mTORC2 protein and decreased phosphorylation of downstream mTORC2 targets.  Our results demonstrate a general dysfunction of the mTORC2 pathway in Mecp2 A140V mice brain and point to developing selective agonists against the mTOR pathway to treat RTT.