MOLECULAR GENETIC ANALYSIS OF FOLATE METABOLISM IN THE ZEBRAFISH(DANIO RERIO)

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Abstract: In order to better understand the role of folic acid in neuronal development, we propose to do a molecular genetic analysis of folate metabolism in the zebrafish(Danio rerio). The zebrafish is an excellent model system in which to analyze the molecular genetics of folate metabolism, since it is a vertebrate embryo that is amenable to a variety of cellular, molecular, and genetic techniques. The nervous system of the zebrafish is simple, and its development has been well described. Most importantly, there have been hundreds of different zebrafish developmental mutants generated. Cloning the genes that encode key regulatory enzymes in folate metabolism and analyzing their sequences and expression patterns in zebrafish mutants with NTDs should be a powerful approach to better understand the underlying mechanisms of NTDs. This information should give us a much better understanding of the molecular genetic basis of NTDs, and should ultimately allow for the design of more efficacious treatments for NTDs. Computer time provided for by this grant will allow for sequence characterization of genes isolated in this study, analysis that is absolutely essential to the success of the study. Achievements - Several genes involved in folate metabolism have been cloned and are now in the process of being analyzed.