Fast skeletal muscle-specific expression of a quail troponin I gene in transgenic mice

Fast skeletal muscle-specific expression of a quail troponin I gene in transgenic mice
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转基因小鼠中鹌鹑肌钙蛋白 I 基因的快速骨骼肌特异性表达

DOI:
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发表时间:
1988
影响因子:
5.3
通讯作者:
A. Peterson
A. Peterson
中科院分区:
生物学2区
文献类型:
--
作者:
P. L. Hallauer;K. Hastings;A. Peterson

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我们已经产生了七个行的转基因小鼠携带鹌鹑基因编码的快速骨骼肌特异性肌钙蛋白I亚型(TCFs)。鹌鹑的DNA包括完整的TcR基因,530个碱基对的5 '侧翼DNA和1.5个碱基对的3'侧翼DNA。在所有七个转基因系中,正常启动和加工的鹌鹑TmRNA在骨骼肌中表达,并在骨骼肌中积累到与鹌鹑肌肉相当的水平。此外,在测试的三个行,鹌鹑TbR mRNA水平在快速骨骼肌(腓肠肌)比在缓慢骨骼肌(比目鱼肌)高许多倍。我们的结论是,细胞机制指导肌纤维类型特异性TdR基因表达介导的顺式调控元件上引入鹌鹑DNA片段,他们控制TdR表达的影响积累的TdR mRNA。这些元素已经在功能上保守,因为鸟类和哺乳动物的进化分歧,尽管存在的主要生理和形态差异之间的鸟类(紧张)和哺乳动物(抽搐)慢肌。在携带多个串联重复拷贝的转基因的转基因小鼠品系中,异常的鹌鹑Tcl3转录物(不同于外显子2上游的正常Tcl3 mRNA)也在某些组织中积累,特别是肺、脑、脾和心脏组织。然而,这种异常的转录本中没有检测到的转基因系只携带一个拷贝的鹌鹑基因。
We have produced seven lines of transgenic mice carrying the quail gene encoding the fast skeletal muscle-specific isoform of troponin I (TnIf). The quail DNA included the entire TnIf gene, 530 base pairs of 5'-flanking DNA, and 1.5 kilobase pairs of 3'-flanking DNA. In all seven transgenic lines, normally initiated and processed quail TnIf mRNA was expressed in skeletal muscle, where it accumulated to levels comparable to that in quail muscle. Moreover, in the three lines tested, quail TnIf mRNA levels were manyfold higher in a fast skeletal muscle (gastrocnemius) than in a slow skeletal muscle (soleus). We conclude that the cellular mechanisms directing muscle fiber type-specific TnIf gene expression are mediated by cis-regulatory elements present on the introduced quail DNA fragment and that they control TnIf expression by affecting the accumulation of TnIf mRNA. These elements have been functionally conserved since the evolutionary divergence of birds and mammals, despite the major physiological and morphological differences existing between avian (tonic) and mammalian (twitch) slow muscles. In lines of transgenic mice carrying multiple tandemly repeated copies of the transgene, an aberrant quail TnIf transcript (differing from normal TnIf mRNA upstream of exon 2) also accumulated in certain tissues, particularly lung, brain, spleen, and heart tissues. However, this aberrant transcript was not detected in a transgenic line which carries only a single copy of the quail gene.