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):

Report Date:

2017-06-01

Pagination or Media Count:

23.0

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 sleepcircadian 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 CRISPRCas9 gene editing of human induced pluripotent stem cells iPSCs to model specific missense mutations of interest and examine their functional consequences in derived neurons.

Subject Categories:

  • Medicine and Medical Research
  • Genetic Engineering and Molecular Biology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE