Nonredundant roles of the elongation factor MEN in postimplantation development

Biochem Biophys Res Commun. 2000 Dec 20;279(2):563-7. doi: 10.1006/bbrc.2000.3970.

Abstract

The MEN/ELL gene was cloned as a fusion partner of the MLL gene in the t(11;19)(q23;p13.1) translocation, which is found in adult myeloid leukemia. MEN belongs to a family of RNA polymerase II elongation factors and dysregulated production of MEN through the MLL promoter could cause malignant transformation of myeloid cells. To pursue the physiological role and determine the requirement of the MEN gene product in mouse development, we generated knockout mice (MEN-/-) by gene targeting in embryonic stem cells. After intercrossing heterozygous mice to generate homozygous mutants, we identified no homozygotes (MEN-/-) even at E9.5, as well as after birth, by Southern analysis. Moreover, histological examinations revealed degenerative changes in nearly one-fourth of E6.5 embryos, which were gradually resorbed by E8.5. Our findings demonstrated that MEN-/- mice are embryonic lethal, and die before E6.5 and after implantation. MEN should play a nonredundant role in postimplantation development of mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Blastocyst / physiology
  • Crosses, Genetic
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Embryonic and Fetal Development*
  • Fetal Death / genetics
  • Heterozygote
  • Homozygote
  • Humans
  • Leukemia, Myeloid / genetics
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Neoplasm Proteins*
  • Peptide Elongation Factors / deficiency
  • Peptide Elongation Factors / genetics
  • Peptide Elongation Factors / metabolism*
  • RNA Polymerase II / metabolism
  • Stem Cells / physiology
  • Transcription Factors / deficiency
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Transcriptional Elongation Factors
  • Translocation, Genetic

Substances

  • DNA-Binding Proteins
  • ELL protein, human
  • Neoplasm Proteins
  • Peptide Elongation Factors
  • Transcription Factors
  • Transcriptional Elongation Factors
  • RNA Polymerase II