Functional Impact of TSC1 Mutations on the Development and Maturation of Inhibitory Cortical Neurons

Abstract

Tuberous sclerosis complex (TSC) is associated with a high rate of epilepsy and autism spectrum disorder (ASD). Mutations in two genes, TSC1 and TSC2, cause TSC. Moreover, these mutations are thought to compromise TSC function in varying ways. Herein, we propose to examine the role of TSC1 in cortical interneurons and will utilize a novel screening assay to determine how human mutations lead to interneuron dysfunction. Our proposal also aims to understand how different types of mutations (i.e., those discovered in cancer versus ASD) differentially alter TSC1 function. Overall, these experiments will help the field understand how TSC individuals may be treated more precisely by understanding how specific TSC1 mutations cause distinct phenotypes. In addition, the information we uncover will help elucidate how dysfunction in TSC1 leads to epilepsy and some symptoms of ASD, potentially leading new therapeutic insights.

Document Details

Document Type
DoD Grant Award
Publication Date
Jan 31, 2017
Source ID
W81XWH1610138

Entities

People

  • John Rubenstein

Organizations

  • United States Army
  • University of California, San Francisco

Tags

Fields of Study

  • Biology

Readers

  • Aquatic Ecology
  • Molecular and Cellular Biology
  • Neuroscience