Project/Area Number |
22700428
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Single-year Grants |
Research Field |
Neurophysiology and muscle physiology
|
Research Institution | Keio University |
Principal Investigator |
|
Project Period (FY) |
2010 – 2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 受容体 / 細胞内シグナル伝達 / 再生分化 / ACVR1 / ALK2 / FOP / 熱ショックプロモーター / メダカ / 骨異形成症 / モデル生物 / ゼブラフィッシュ / トランスジェニック / Cre loxP / 熱ショックタンパク |
Research Abstract |
Fibrodysplasia ossificans progressiva(FOP) is a genetic disorder of dysregulated cellular differentiation which causes fibrous tissue(including muscle, tendon, and ligament) to be ossified when damaged. The mutations were identified in the activin A receptor, type I(ACVR1), a BMP type-1receptor. This study was purposed to establish the transgenic medaka fish that can induce overexpression of the ACVR1or BMP4gene by heat-shock in any target time points, tissues and cells. I established heat-shock inducible Cre recombinase expressing transgenic medaka fish(hsp70b :: Cre) using endogenous hsp70promoter and Cre inducible myogenic cells specific ACVR1expressing transgenic fish(DES :: lGlBMP4). However, both of heat-shock treated and non-treated double transgenic medaka fishes(hsp70b :: Cre and DES :: lGlBMP4) exhibited FOP like phenotypes, which mean endogenous hsp70 promoter was expressed continuously at a low level without heat induction. Then I combined the dual promoter expressing system and artificial heat-shock promoter and established heat-inducible double transgenic medaka fish(8xHSE :: Cre x DES : lGlACVR1).
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