| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
Transgenic mice carrying human tyrosine hydroxylase(TH)gene have been produced and analyzed. The transgene was expressed tissue-specifically in the brain and adrenal medulla. It was found that the tissue homogenate from transgenic(Tg)striatum had the enzyme activity about 3-fold higher than that from non-Tg striatum, but the dopamine content of the striatum was remained unchanged. To understand the mechanism of this discrepancy, both in situ and in vivo studies were carried out using tissue slice system or in vivo microdialysis. The data show that some possible mechanisms were denied, which include the reduced level of phosphorylation of TH molecule, insufficient amount of cofactor tetrahydrobiopterin in Tg striatum, and accelerated turnover of dopamine in Tg mice, From these experiment, feed-back inhibition of the enzyme activity by the product, dopamine, seems to be more likely in the Tg striatum to keep the in vivo enzyme activity almost unchanged.
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