Accession Number : AD1050350

Title :   NF1 Neuronal Genotype-Phenotype Relationships

Descriptive Note : Technical Report,01 Jun 2016,31 May 2017

Corporate Author : Massachusetts General Hospital Boston United States

Personal Author(s) : Walker, James A

Full Text :

Report Date : 01 Jun 2017

Pagination or Media Count : 23

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.

Descriptors :   genetic disorders , mutations , neurons , stem cells

Subject Categories : Medicine and Medical Research
      Genetic Engineering and Molecular Biology

Distribution Statement : APPROVED FOR PUBLIC RELEASE