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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 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.

Pubmed ID: 7958896

Authors

  • Chen Z
  • Friedrich GA
  • Soriano P

Journal

Genes & development

Publication Data

October 1, 1994

Associated Grants

  • Agency: NICHD NIH HHS, Id: HD24875

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • DNA Primers
  • DNA, Complementary
  • DNA-Binding Proteins
  • Embryo, Mammalian
  • Female
  • Fetal Death
  • Genes, Lethal
  • Heart Defects, Congenital
  • Male
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins
  • Retroviridae
  • Stem Cells
  • Transcription Factors