Nonredundant roles of the elongation factor MEN in postimplantation development
Autor: | Kinuko Mitani, Hiroaki Honda, Hideaki Oda, Tetsuya Yamagata, Motoshi Ichikawa, Chika Iida, Takashi Asai, Hisamaru Hirai, Kazuhiro Maki, Mineo Kurokawa |
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Rok vydání: | 2000 |
Předmět: |
Adult
Heterozygote Mutant Biophysics Mice Inbred Strains Biology Biochemistry Translocation Genetic Gene product Embryonic and Fetal Development Mice medicine Animals Humans Molecular Biology Gene Fetal Death Crosses Genetic Mice Knockout Stem Cells Homozygote Gene targeting Myeloid leukemia Cell Biology medicine.disease Peptide Elongation Factors Molecular biology Neoplasm Proteins Elongation factor DNA-Binding Proteins Leukemia Blastocyst Leukemia Myeloid Knockout mouse RNA Polymerase II Transcriptional Elongation Factors Transcription Factors |
Zdroj: | Biochemical and biophysical research communications. 279(2) |
ISSN: | 0006-291X |
Popis: | 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. |
Databáze: | OpenAIRE |
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