TRANSCRIPTIONAL ENHANCER FACTOR-1 DISRUPTION BY A RETROVIRAL GENE TRAP LEADS TO HEART-DEFECTS AND EMBRYONIC LETHALITY IN MICE

We have used a retroviral gene trap in embryonic stem (ES) cells to de rive a recessive embryonic lethal mouse strain, ROSA beta-geo5. Mutant embryos display an enlarged pericardial cavity, brachycardia, a dilat ed fourth ventricle in the brain, and die between embryonic days 11 an d 12. Whereas heart development in the mutant embryos is extensive, th e ventricular wall is abnormally thin with a reduced number of trabecu lae. Cloning of the trapped gene indicates that proviral insertion cre ates a null mutation in the transcriptional enhancer factor 1 (TEF-1) gene. Although transcription of a number of muscle-specific genes beli eved to be TEF-1 targets appears normal, the defect in cardiogenesis i s likely attributable to diminished transcription of one or several ca rdiac-specific genes.