Establishment of model mouse susceptible to human prion; Visualization of the molecular interaction of prion protein in vivo

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We attempted to establish the model mice, which were highly susceptible for human prion and enabled the visualization of molecular interaction of prion protein (PrP) in vivo, especially conversion of normal cellular PrP into abnormal prion (PrPsc) by transgenic techniques. The constructs were designed to encode the fusion protein composed of chimeric protein which was composed of N-terminal sequences from mouse and main ORF region from human PrPc and Fluorescent protein (FP). As C-terminal sequences were deleted from human PrPc, the fusion protein derived from the transgene was expected to be secretary form. Four (EGFP-mouse/human chimeric PrP) and five (EBFP-mouse/human chimeric PrP) transgenic lines were produced. The transgenic mice showed expression of the transgene in the general organs, and high expression in the brain. Both the level of transgene expression and 1he processing of gene products was expected to be similar to that of endogenous mouse prion, as the regulatory region of the transgene were derived from mouse genome. Unfortunately, this project was suspended as inoculation of PrPsc revealed that the transgenic mice carrying the transgene encoding secretary mouse/human chimeric PrP were not susceptible for human prion in our latest collaborative study [Kitamoto (Tohoku University), Mohri (Kyushu University) and Miyoshi, unpublished data]. Our previous collaborative study indicated the mice expressing mouse/human chimeric PrP was highly susceptible to human prion [Kitamoto (Tohoku University), Mohri (Kyushu University) and Miyoshi, unpublished data], however, modification of the molecule into secretary form was not effective to enhance the susceptibility.