Developing a Zebrafish Model of NF1 for Structure-Function Analysis and Identification of Modifier Genes
Revised final rept. 1 Apr 2007-31 Mar 2012
PENNSYLVANIA UNIV PHILADELPHIA
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This final report summarizes the activity of this project which was focused on the identification and characterization of the zebrafish orthologs of the neurofibromatosis type 1 NF1 gene. This project involved work within the Epstein laboratory and collaboration with the laboratory of Dr. Thomas Look at the Dana Farber Cancer Institute as a sub-contract. This report summarizes the collaborative work including results from both groups. Significant progress was made toward the proposed aims and several publications resulted from the work. The major discoveries included the isolation and characterization of two zebrafish orthologs, nf1a and nf1b. The genes have been sequenced and their expression patterns identified. Gene knockdown phenotypes have been characterized and include overgrowth of glia and cardiovascular abnormalities. Perhaps most critically, independent and compound mutations in these genes have been engineered in zebrafish using zinc finger nucleases producing germ-line transmission of the mutations. Thus, critical reagents and a new animal model of type 1 neurofibromatosis has been produced which is amenable to high throughput drug and genetic screening.
- Genetic Engineering and Molecular Biology