| Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2013: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2012: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Research Abstract |
Mutations of genes (CHRNA4, CHRNB2, or CHRNA2) of neuronal nicotinic ACh receptor (nAChR) cause autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) in human. ADNFLE-related seizures are seen exclusively during slow wave phase sleep. We generated transgenic rat strains that harbor a missense mutation S286L rat Chrna4 gene, which had been identified in CHRNA4 in ADNFLE with Cre gene (S286L-TG). S286L-TG was free of biological abnormalities, such as dysmorphology in CNS, and behavioral abnormalities. To clarify the effects of S286L mutantion on epileptogenesis and ictogenesis of ADNFLE, after ADNFLE onset, S286L-TG was administrated tamoxifen (Cre inducer agent). The degradation of S286L mutant Chrna4 induced by Cre did not affect ADNFLE seizures. These results suggest that S286L mutant Chrna4 gene probably plays important roles in the development of epileptogenesis, but did not affect ictogenesis.
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