NF1 Neuronal Genotype-Phenotype Relationships
Abstract
This project examines pathogenic NF1 missense mutations. We have modeled these mutations in Drosophila transgenes in order to investigate their molecular and cellular consequences in vivo. We have examined their ability to rescue Ras signaling in neurons in Drosophila deficient for endogenous NF1. Further, we have assessed their ability to rescue NF1 mutant developmental and adult-specific defects, including organismal growth, climbing ability and sleep/circadian behaviors. These assays have identified previously unexplored regions of the neurofibromin protein that are required for correct function in Drosophila. We will use these insights for subsequent CRISPR/Cas9 gene editing of human induced pluripotent stem cells (iPSCs) to model specific missense mutations of interest and examine their functional consequences in derived neurons.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2017
- Accession Number
- AD1050350
Entities
People
- James A. Walker
Organizations
- Massachusetts General Hospital