Engert J C, Servaes S, Sutrave P, Hughes S H, Rosenthal N
Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown 02129, USA.
Nucleic Acids Res. 1995 Aug 11;23(15):2988-94. doi: 10.1093/nar/23.15.2988.
In transgenic mice, muscle-specific expression of the c-ski oncogene induces hypertrophy exclusively in a subset of fast muscle fibers. Here we report that regulatory elements from two genes expressed in fast fibers, myosin light chain 1/3 (MLC) and muscle creatine kinase (MCK), were activated when co-transfected with c-ski expression vectors in myoblasts. The expression from the MLC enhancer was reduced when the c-ski oncogene was cotransfected with MyoD into NIH3T3 fibroblasts. Activation of the MLC enhancer by Ski also occurred in vivo, since bigenic progeny generated by mating MLC-CAT and MSV-skitransgenic mice displayed higher CAT activity in their muscles than did the MLC-CAT parental line. Identification of gene targets for the fiber-specific action of the c-ski gene product provides a molecular model that could be used for the further dissection of Ski-induced hypertrophy, both in tissue culture and in vivo.
在转基因小鼠中，c-ski癌基因的肌肉特异性表达仅在一部分快肌纤维中诱导肥大。我们在此报告，当与c-ski表达载体共转染到成肌细胞中时，在快肌纤维中表达的两个基因，肌球蛋白轻链1/3（MLC）和肌肉肌酸激酶（MCK）的调控元件被激活。当c-ski癌基因与MyoD共转染到NIH3T3成纤维细胞中时，MLC增强子的表达降低。Ski对MLC增强子的激活在体内也会发生，因为通过交配MLC-CAT和MSV-ski转基因小鼠产生的双基因后代在其肌肉中显示出比MLC-CAT亲本品系更高的CAT活性。鉴定c-ski基因产物纤维特异性作用的基因靶点提供了一个分子模型，可用于在组织培养和体内进一步剖析Ski诱导肥大的机制。
