Overexpression of myogenic regulatory factors driven by heat shock promoters in medaka and its developmental study.

进行性骨化性纤维发育不良（FOP）是一种细胞分化失调的遗传性疾病，其导致纤维组织（包括肌肉、肌腱和韧带）在受损时骨化。这些突变是在激活素A受体I型（ACVR 1）中发现的，ACVR 1是BMP 1型受体。本研究的目的是建立转基因青鳉鱼，通过热休克诱导ACVR 1和BMP 4基因在任意时间点、组织和细胞中的过表达。本研究利用内源性热休克蛋白70启动子和Cre诱导型肌细胞特异性表达ACVR 1的转基因鱼（DES：：lGlBMP 4），建立了表达热休克诱导型Cre重组酶的转基因青鳉鱼（hsp70 b：：Cre）。而热休克处理和未处理的双转基因青鳉鱼（hsp70 b：：Cre和DES：：lGlBMP 4）均表现出FOP样表型，表明内源性hsp70启动子在无热诱导的情况下持续低水平表达。然后将双启动子表达系统与人工热激启动子相结合，建立了热诱导型双转基因青鳉鱼（8xHSE：：Cre x DES：lGlACVR 1）。

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).