Establishing the Molecular Basis of the Neurodevelopmental Features of TSC
Abstract
Tuberous sclerosis complex (TSC) is a dominant genetic disorder caused by mutations in the genes TSC1 and TSC2 and characterised by benign tumours in multiple organs. The neurological manifestations of TSC, including epilepsy and autism, have a particularly early onset and have the greatest morbidity. Mutations in Tsc1/2 result in activation of the highly conserved mechanistic target of rapamycin (mTOR) pathway. We recently identified the protein Unkempt as the first downstream component of the mTOR pathway to regulate neuronal differentiation in Drosophila. In this project we are testing the hypothesis that Unkempt is a key downstream regulator of mTOR complex 1 (mTORC1) in the developing mammalian nervous system and that mis-regulation of Unkempt contributes to the neurological manifestations of TSC. During this research period we have validated an Unkempt phospho-specific antibody that we have generated and made progress towards testing the role of Unkempt phosphorylation in vivo and analysing Unkempt phosphorylation in a mouse model of TSC.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2022
- Accession Number
- AD1217524
Entities
People
- Carl Hobbs
- Joseph M. Bateman
- Pranetha Baskaran
Organizations
- King's College London