Z. Chen et al., TRANSCRIPTIONAL ENHANCER FACTOR-1 DISRUPTION BY A RETROVIRAL GENE TRAP LEADS TO HEART-DEFECTS AND EMBRYONIC LETHALITY IN MICE, Genes & development, 8(19), 1994, pp. 2293-2301
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.