The function of genes in pattern formation, organogenesis, and developmental physiology of living organisms needs to be uncovered and the best current tools to accomplish these goals are likely a mutational analysis of several model animals. In this project, we are working to identify and characterize the neuron-specific zebrafish genes using chemical mutagenesis approach with ENU(1-ethyl-1-nitrosourea), aiming to provide some clues to human neural-specific genes, and more importantly, neural disease-causing genes. Sequence comparison showed that zebrafish has 85% homology in nucleotides and amino acid to the human and developmental pathway is well conserved. Study for human functional genomics may take advantage of zebrafish's well-established developmental system and genetics and transgenesis. Unlike general screens in which a broad range of mutant phenotype is sought, aiming at the isolation for large-scale neuron-specific mutants of zebrafish, we plan to utilize the transgenic zebrafish containing a neuron-specific HuC(p)-GFP fusion construct in stead of using conventional wild-type strain, enabling to efficiently screen the neural-defective mutants

We are now concentrating on screening and characterizing the neuronal-defective zebrafish mutants carrying HuC(p)-GFP construct and were so far able to identify dozens of possible neuron-specific mutants by extensive screening of the zebrafish mutants and will continue to characterize these mutants by genetic and physical analysis. Considering that the high homology between human and zebrafish in nucleotides and amino acids sequence, it is a realistic approach to apply the information obtained from zebrafish study to the human system. We expect to use this strategy to identify human neuron-specific genes and hopely make backgrounds for designing the antagonizing products to cure the neural diseases.

In addition, zebrafish are very useful vertebrate model not only for embryology and developmental biology but also a model for genetic analysis. It is well known that other vertebrates, such as the mouse and Xenopus develop rather slowly and the mouse develops in uterus and therefore cannot be used as a good model for embryonic development. Besides to their unique advantage of rapid development and transparent embryos, zebrafish brain and nervous system development is similar to that of other vertebrates. They provide important questions such as the role of genetics in brain and nervous system development on complex organisms such as vertebrates. Therefore they have become such an important animal model system compared to already established models for screening drug targets, oncogene analysis and so on.

We are planning to construct the transgenic zebrafish which can be used as an animal model system to test various drug candidates, possible oncogenes by constructing specific transgenic zebrafish. Using Zebrafish as an animal model system will be very demanding world-wide and we feel very comfortable in that the knowledge and know-how to make a transgenic zebrafish will be useful in elucidating the function and role of specific targets .

 

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