CARDIAC MYOSIN HEAVY-CHAIN MESSENGER-RNA EXPRESSION AND MYOCARDIAL-FUNCTION IN THE MOUSE HEART
CARDIAC MYOSIN HEAVY-CHAIN MESSENGER-RNA EXPRESSION AND MYOCARDIAL-FUNCTION IN THE MOUSE HEART
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DOI：
10.1161/01.res.68.6.1742
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发表时间：
1991-06-01
影响因子：
20.1
通讯作者：
ROBBINS, J
中科院分区：
文献类型：
--
作者：
NG, WA;GRUPP, IL;ROBBINS, J
脊椎动物的心脏包含两种肌球蛋白重链亚型，α和β，这两种亚型的表达存在差异。为了建立基因打靶实验的小鼠模型，我们定义了肌球蛋白亚型在心脏发生过程中的精确时间表达，并获得了心脏性能的定量测量。通过从发育过程中的CD-1小鼠心脏分离RNA，并将其与专门检测α或β心肌肌球蛋白重链mRNAs的探针杂交，确定了α和β心脏转录本的相对水平。数据表明，虽然这两种异构体从心脏发生开始就存在，但β-异构体在胚胎发育和胎儿发育期间占主导地位。这种关系在出生第一天后被逆转，在转换过程中绝对转录水平显著下降；新生儿保持16：1的α/β比率，在成年阶段保持相对较高的α-转录水平。为了能够在正常小鼠和转基因小鼠之间进行功能比较，我们获得了正常和低动力小鼠心脏的分离逆行灌流和工作心脏准备中的心肌功能指数。我们发现，小鼠心脏的生理学与大鼠心脏相似，因为我们观察到小鼠朗宁多夫制剂的力-频率关系中有一个正阶梯。我们还看到了由成对刺激和持续性后收缩增强引起的超过两倍的对照组的收缩反应。与大鼠的情况一样，在工作状态下的小鼠心脏中，后负荷(Starling阻力，压力)的变化比前负荷(容量，静脉回流)的变化产生更陡峭的Starling功能曲线。
The vertebrate heart contains two myosin heavy chain isoforms, alpha and beta, which are differentially expressed. To establish a murine model for gene-targeting experiments, we defined the precise temporal expression of the myosin isoforms during cardiogenesis and obtained quantitative measurements of cardiac performance. The relative levels of the alpha- and beta-cardiac transcripts were determined by isolating the RNA from the hearts of CD-1 mice during development and hybridizing the preparations to probes that detect specifically the alpha- or beta-cardiac myosin heavy chain mRNAs. The data indicate that, although both isoforms are present from the onset of cardiogenesis, the beta-isoform predominates during embryogenesis and fetal development. This relation is reversed after the first day of life with a significant drop in the absolute transcript levels during the switch; and alpha/beta ratio of 16:1 is maintained in the neonate, and the relatively high levels of the alpha-transcript remain throughout the adult stages. To be able to make functional comparisons between normal and transgenic mice, we obtained indexes of myocardial function in isolated retrogradely perfused and in work-performing heart preparations in normal and hypodynamic mouse hearts. We found that the physiology of the mouse heart is similar to the rat heart in that we observed a positive staircase in the force-frequency relation of the mouse Langendorff preparation. We also saw contractile responses of more than twice control induced by paired stimulation and persistent postextrasystolic potentiation. As is the case for the rat, in the work-performing mouse heart, afterload (Starling resistance, pressure) changes produced a steeper Starling function curve than did changes in preload (volume, venous return).