Ojala J, Choudhury M, Bag J
Department of Molecular Biology and Genetics, University of Guelph, Ontario, Canada.
Antisense Nucleic Acid Drug Dev. 1997 Feb;7(1):31-8. doi: 10.1089/oli.1.1997.7.31.
The effect of blocking expression of a specific gene with antisense phosphodiester oligodeoxynucleotides on the coordinate regulation of myogenesis was studied. Different regions of both fast and slow troponin C (TnC) mRNAs were targeted for binding of the antisense oligomer. The 5'-cap region of both mRNAs was found to be the most effective target for inhibiting the expression of these genes. Approximately 40%-60% inhibition of expression of a specific isoform of TnC was achieved. However, inhibition of the TnC expression did not appreciably alter the pattern of myogenesis of mouse C2C12 cells. The differentiated murine muscle cells were able to cope with this reduced level of the target gene expression by antisense phosphodiester oligomers. We have also used a phosphorothioate oligomer targeted against a common sequence within the coding region of both fast and slow TnC mRNAs. This oligomer was found to be ineffective in blocking TnC gene expression.
研究了用反义磷酸二酯寡脱氧核苷酸阻断特定基因表达对肌生成协同调节的影响。针对快、慢肌钙蛋白C（TnC）mRNA的不同区域，使反义寡聚物与之结合。发现两种mRNA的5′-帽区是抑制这些基因表达的最有效靶点。实现了对特定TnC同工型表达约40%-60%的抑制。然而，TnC表达的抑制并未明显改变小鼠C2C12细胞的肌生成模式。分化的小鼠肌肉细胞能够通过反义磷酸二酯寡聚物应对靶基因表达的这种降低水平。我们还使用了一种硫代磷酸酯寡聚物，其靶向快、慢TnC mRNA编码区内的一个共同序列。发现这种寡聚物在阻断TnC基因表达方面无效。
