| Project/Area Number |
08680855
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Tokyo Institute of Psychiatry |
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Principal Investigator |
NUKADA Toshihide Tokyo Institute of Psychiatry, Department of Neurochemistry, Head of Department, 神経化学研究部門, 副参事研究員 (80189349)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Potassium channel / G-protein / sulfonylures receptor / K_<ATP> / Transgenic mouse / Ted expression system / ムスカリン性K^+チャンネル / 内向き整流性K^+チャンネル / BIRチャンネル / GIRK1チャンネル / テトラサイクリン反応性発現 |
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| Research Abstract |
To understand the physiological roles of G-protein-coupled potassium channels in brain, transgenic mice expressing K_<ATP> (Kir 6.2) and sulfonylurea receptor (SUR1) were generated. Kir 6.2 or SUR1 cDNA was inserted downstream of the tetracycline-regulated promoter region as the transgene vector, and the expression unit was excised from the resulting plasmid. These expression units were microinjected into fertilized eggs of BDF1 mice by the standard procedures. Transgenic mice were selected from possible founders by polymerase chain reaction and Southern blot analysis, ans were backcrossed to BDF1 mice. Two transgenic lines were established. To regulate the expression of Kir 6.2 and SUR1 by tetracycline, two transgenic lines overexlpressing O binding transactivator (tTA) were also established. Litter sizes and postneonatal development were indistinguishable from nontransgenic litter-mate controls in Kir 6.2-transgenic lines. However, both two SUR1-transgenic lines showed growth retardation and subsequent neonatal death, which were severer in homozygous mutant mice than in heterozygous mice. Thus, it was suggested that the transgenic phenotype was due to transgenic expression of SUR1, and not due to an insertional effect. In order to reveal the primary cause of death, we are now investigating the mutant mice in both pathological and biochemical aspects, in particular, focusing on the plasma levels of insulin and glucose.
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