CARDIOMYOCYTE PROLIFERATION IN MICE EXPRESSING ALPHA-CARDIAC MYOSIN HEAVY CHAIN-SV40 T-ANTIGEN TRANSGENES
CARDIOMYOCYTE PROLIFERATION IN MICE EXPRESSING ALPHA-CARDIAC MYOSIN HEAVY CHAIN-SV40 T-ANTIGEN TRANSGENES
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DOI：
10.1152/ajpheart.1992.262.6.h1867
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发表时间：
1992-06-01
影响因子：
--
通讯作者：
FIELD, LJ
中科院分区：
文献类型：
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作者：
KATZ, EB;STEINHELPER, ME;FIELD, LJ
为了确定成年心肌细胞的增殖能力，我们培育了在心脏中表达SV40大T抗原癌基因的转基因小鼠。由大鼠α-心肌肌球蛋白重链启动子和SV40早期区域组成的融合基因被用于将癌基因表达靶向心肌。成年转基因动物的心房和心室肌细胞均有SV40大T抗原的表达。T抗原的表达与靶细胞的增殖有关。免疫组织化学分析表明，增殖细胞继续表达肌节肌球蛋白。电子显微镜观察表明，处于细胞周期不同阶段的心肌细胞在体内保留了典型的有丝分裂心肌细胞的超微结构特征。从转基因肿瘤分离的心肌细胞能够在培养中增殖，并保持分化的表型，自发收缩活动证明了这一点。初步研究表明，在保留这种分化表型的同时，这些细胞可以进行有限的传代。这些研究表明，转基因小鼠的心室和心房心肌细胞在靶向T抗原表达后都会增殖。
To determine the proliferative potential of adult ventricular cardiomyocytes, we have generated transgenic mice that express the SV40 large T-antigen oncogene in the heart. A fusion gene comprised of the rat alpha-cardiac myosin heavy chain promoter and the SV40 early region was used to target oncogene expression to the myocardium. Expression of SV40 large T-antigen was observed in both atrial and ventricular cardiomyocytes in adult transgenic animals. T-antigen expression was associated with hyperplasia in the targeted cells. Immunohistological analysis indicated that the proliferating cells continued to express sarcomeric myosin. Electron microscopic examination demonstrated that cardiomyocytes in various stages of the cell cycle retained ultrastructural characteristics typical of mitotic cardiac muscle cells in vivo. Cardiomyocytes isolated from transgenic tumors were able to proliferate in culture and retained a differentiated phenotype, as evidenced by spontaneous contractile activity. Preliminary studies indicate that these cells can undergo a limited number of passages while retaining this differentiated phenotype. These studies demonstrate that both ventricular and atrial cardiomyocytes from transgenic mice proliferate in response to targeted T-antigen expression.