Analysis of molecular basis of mouse prefrontal cortex function

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This research aimed to clarify a molecular basis of prefrontal cortex function in the learning process by using the gene manipulation mouse. To manipulate the gene function in the mouse prefrontal cortex-selective manner, we first screened prefrontal cortex-selective expressing genes by suppressive subtractive hybridization method. Then, we confirmed the prefrontal-selective expression of the dopamine D4 receptor gene by the mRNA in situ hybridization. Next, we obtained the bacterial artificial chromosome (BAG) including the mouse genomic D4R gene from the CHORI BACPAC resources. We improved the method of homologous recombination in E.coli.and established the efficient protocol for constructing the BAC-based transgenic vector and gene targeting vector (TV) in embryonic stem (ES) cells. Using our improved protocol, we introduced the dominant negative NMDA-type glutamate receptor subunit GluRζ(N/R) in the D4R locus of the BAG. We have tried to introduce modified D4R BAG into the mouse prefrontal cortex by the DNA electroporation, and we also tried to establish the transgenic mouse of modified D4R-BAC and ES cells.