Yang Maozhou, Jiang Hong, Li Li
Int J Physiol Pathophysiol Pharmacol. 2010;2(1):12-9. Epub 2009 Nov 22.
SM22α, also known as SM22, has been widely used as a smooth muscle cell (SMC) marker and is known to be expressed in the embryonic heart. The intron 1 of Sm22 contains multiple important and evolutionarily conserved regulatory elements. To determine the role of the intron 1 in Sm22 transcriptional regulation and the function of SM22 during development, we generated a Sm22 knockout mouse by replacing the intron 1 and the translation initiation with a nuclear localized LacZ (nLacZ) reporter. The resulting Sm22 knockout mice (Sm22(-)/(-)) were viable and fertile without any apparent developmental defects. Using X-gal staining assay, we found that Sm22 transcription was detectable in the chorion formation region and in the heart field before formation of the heart tube at E7.5, namely much earlier than the looped heart stage where it had been previously reported. The expression of lacZ progressively expanded throughout the heart tube by E8.5. LacZ was transiently expressed in the heart and somites and then became restricted to the vascular and visceral SMC organs. These results indicate that SM22 is not required for mouse basal homeostatic function and that the intron 1 is dispensable for Sm22 transcription during development. Given the importance of vasculature in organogenesis and in diseases, this mouse line may be a valuable tool to trace the development and pathology of the cardiovascular system.
SM22α,也被称为SM22,已被广泛用作平滑肌细胞(SMC)标志物,并且已知在胚胎心脏中表达。Sm22的内含子1包含多个重要且在进化上保守的调控元件。为了确定内含子1在Sm22转录调控中的作用以及SM22在发育过程中的功能,我们通过用核定位的LacZ(nLacZ)报告基因替换内含子1和翻译起始位点,构建了一只Sm22基因敲除小鼠。所得到的Sm22基因敲除小鼠(Sm22(-)/(-))能够存活且可育,没有任何明显的发育缺陷。通过X-gal染色分析,我们发现在胚胎第7.5天心脏管形成之前,在绒毛膜形成区域和心脏场中可检测到Sm22转录,即比之前报道的环状心脏阶段要早得多。到胚胎第8.5天时,lacZ的表达在整个心脏管中逐渐扩展。LacZ在心脏和体节中短暂表达,然后局限于血管和内脏SMC器官。这些结果表明,SM22对于小鼠基础稳态功能并非必需,并且内含子1在发育过程中对于Sm22转录是可有可无的。鉴于脉管系统在器官发生和疾病中的重要性,该小鼠品系可能是追踪心血管系统发育和病理学的一个有价值的工具。