2010 Fiscal Year Final Research Report
Downregulation of sodium channel β4 subunit in Huntington Disease transgenic mice
| Project/Area Number |
20500329
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
OYAMA Fumitaka The Institute of Physical and Chemical Research, 工学部, 教授 (40194641)
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| Project Period (FY) |
2008 – 2010
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| Keywords | ナトリウムチャネルベータ4 / ハンチントン病 / モデルマウス / 蛍光タンパク質 / ベータ4プロモーター / 遺伝子発現抑制 |
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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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[Journal Article] A functional null mutation of SCN1B in a patient with Dravet syndrome.2009
Author(s)
Patino G.A., Claes L.R., Lopez-Santiago L.F., Slat E.A., Dondeti R.S., Chen C., O'Malley H.A., Gray C.B., Miyazaki H., Nukina N., Oyama F., De Jonghe P., Isom L.L.
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Journal Title
J.Neurosci. 29
Pages: 10764-10778
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[Journal Article] Genetically determined differences in sodium current characteristics modulate conduction disease severity in mice with cardiac sodium channelopathy.2009
Author(s)
Remme C.A., Scicluna B.S., Verkerk A.O., Amin A.S., Van Brunschot S., Beekman L., Deneer V.H.M., Chevalier C., Oyama F., Miyazaki H., Nukina N., Wilders R., Escande D., Houlgatte R., Wilde A.A.M., Tan H.L., Veldkamp M.W., de Bakker J.M.T., Bezzina C.R.
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Journal Title
Circulation Res. 104
Pages: 1283-1292
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