Early embryonic lethality caused by targeted disruption of the mouse selenocysteine tRNA gene ( <i>Trsp</i> )

• Michael R. Bösl

  Banyu Tsukuba Research Institute (Merck), Tsukuba 300-26, Japan; and Laboratory of Biomedical Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, 113, Japan

• Kazuaki Takaku

  Banyu Tsukuba Research Institute (Merck), Tsukuba 300-26, Japan; and Laboratory of Biomedical Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, 113, Japan

• Masanobu Oshima

  Banyu Tsukuba Research Institute (Merck), Tsukuba 300-26, Japan; and Laboratory of Biomedical Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, 113, Japan

• Susumu Nishimura

  Banyu Tsukuba Research Institute (Merck), Tsukuba 300-26, Japan; and Laboratory of Biomedical Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, 113, Japan

• Makoto M. Taketo

  Banyu Tsukuba Research Institute (Merck), Tsukuba 300-26, Japan; and Laboratory of Biomedical Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, 113, Japan

抄録

Selenoprotein biosynthesis is mediated by tRNA Sec , which inserts selenocysteine at UGA codons in a complex, context-specific manner. This opal suppressor serves in the conversion of serine to selenocysteine as well. The mouse tRNA Sec gene ( Trsp ) maps to a proximal segment of chromosome 7. We constructed mice carrying a targeted deletion of the Trsp gene. The heterozygous mutants were viable, fertile, and appeared normal. Although the level of tRNA Sec was reduced to about 50%–80% of the wild type in most organs, one of the selenoproteins, glutathione peroxidase, remained unaffected in the levels of its mRNA, protein, and enzyme activity, indicating that the haploid amount of tRNA Sec is not limiting in its biosynthesis. In contrast, the homozygous mutants died shortly after implantation, and the embryos were resorbed before 6.5 days post coitum. When the preimplantation embryos were placed in culture, however, the trophoectoderm cells showed outgrowths and the inner cell mass cells of the homozygous embryos were able to proliferate. These results indicate that Trsp expression is essential for early development of the embryo, and its lack causes peri-implantation lethality. However, the lethality does not appear to be due to a cell-autonomous function of tRNA Sec .

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 94 (11), 5531-5534, 1997-05-27

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1363107370261675904
• NII論文ID: 80009716096
• DOI: 10.1073/pnas.94.11.5531
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.94.11.5531
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