Chen Z, Friedrich G A, Soriano P
Program in Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Genes Dev. 1994 Oct 1;8(19):2293-301. doi: 10.1101/gad.8.19.2293.
We have used a retroviral gene trap in embryonic stem (ES) cells to derive a recessive embryonic lethal mouse strain, ROSA beta-geo5. Mutant embryos display an enlarged pericardial cavity, bradycardia, a dilated fourth ventricle in the brain, and die between embryonic days 11 and 12. Whereas heart development in the mutant embryos is extensive, the ventricular wall is abnormally thin with a reduced number of trabeculae. Cloning of the trapped gene indicates that proviral insertion creates a null mutation in the transcriptional enhancer factor 1 (TEF-1) gene. Although transcription of a number of muscle-specific genes believed to be TEF-1 targets appears normal, the defect in cardiogenesis is likely attributable to diminished transcription of one or several cardiac-specific genes.
我们利用胚胎干细胞（ES细胞）中的逆转录病毒基因捕获技术获得了一种隐性胚胎致死小鼠品系ROSA beta-geo5。突变胚胎表现出心包腔扩大、心动过缓、脑内第四脑室扩张，并在胚胎第11至12天之间死亡。尽管突变胚胎的心脏发育广泛，但心室壁异常薄，小梁数量减少。捕获基因的克隆表明，前病毒插入在转录增强因子1（TEF-1）基因中产生了无效突变。虽然一些被认为是TEF-1靶标的肌肉特异性基因的转录看起来正常，但心脏发生缺陷可能归因于一个或几个心脏特异性基因的转录减少。
