Developing a Zebrafish Model of NF1 for Structure-Function Analysis and Identification of Modifier Genes
Abstract
The primary goal of this project is to develop a zebrafish model of the autosomal dominant genetic disorder type I neurofibromatosis (NF1). This disorder is very common, affecting approximately 1 in 3000 live births, and results from mutations in the NF1 gene. A zebrafish model of this disease will be particularly useful in furthering our understanding of the pathophysiology of this disorder and will allow the application of high throughput strategies to screen libraries of chemical compounds to identify small molecules that may prove efficacious in modulating NF1-associated phenotypes. The zebrafish model will also allow for rapid and cost-effective structure-function analysis of neurofibromin, the large protein product of the NF1 gene. Zebrafish develop rapidly and are transparent throughout early development allowing for the easy visualization of many developing tissues, including the cardiovascular and nervous systems. In addition, the availability of transgenic reporter lines that express fluorescent proteins under the control of tissue-specific promoters allows for real-time visualization of complex developmental processes. This model system is also tenable to forward genetic screens, which will allow for the identification of enhancers and suppressors of NF1 phenotypes in an unbiased fashion. Prior to the efforts funded by this award, the zebrafish orthologues of the human NF1 gene had not been described or characterized. This project involves the collaboration of two established groups to coordinate efforts in developing and exploiting a zebrafish model of this important genetic disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2010
- Accession Number
- ADA554538
Entities
People
- Jonathan A. Epstein
Organizations
- University of Pennsylvania