| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Research Abstract |
Sodium channel β4 (β4) is a recently identified auxiliary subunit of the voltage gated-sodium channels. We identified β4 as an EST that was significantly downregulated in the striatum of Huntington Disease (HD) model mice and patients. To define the molecular mechanism underlying the reduction of β4 expression, we generated transgenic mouse line expressing Venus under the control of mouse β4 promoter in brain. We established six mice lines exhibiting Venus expression primarily in striatum, cortex or both striatum and cortex. The mouse line exhibiting predominant Venus expression in striatum was crossed with HD model mice to generated double transgenic mice. The expression of Venus transcribed from β4 promoter-Venus transgene lacking exon-intron structure and 3'-UTR as well as endogenous β4 was downregulated in the striatum of double transgenic mice. Venus expression was reduced in nuclear accumulation (NA) of the expanded polyglutamine bearing cells, whereas it was preserved in non-NA bearing cells. These results indicate that downregulation of β4 in HD model mice is dependent on its promoter and nuclear accumulation (NA) of the expanded polyglutamine.
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