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Essential role of S-adenosylmethionine decarboxylase in mouse embryonic development
Kazuhiro Nishimura1, Fubito Nakatsu, Keiko Kashiwagi
1Graduate School of Pharmaceutical Sciences, Chiba University, 1-33, Yayoi-cho, Inage-ku, Chiba, 263-8522, Japan.
Background:
S-Adenosylmethionine decarboxylase (AdoMetDC) is one of the key enzymes involved in the biosynthesis of spermidine and spermine, which are essential for normal cell growth. To examine the role of polyamines in embryogenesis, we carried out targeted disruption of the mouse Amd1 gene, encoding AdoMetDC, to generate mice that can not synthesize spermidine and spermine.
Results:
Amd1 heterozygous mice were viable, normal and fertile. However, homozygous Amd1(-/-) embryos died early in embryonic development, between E3.5 and E6.5 days post-coitus. Homozygous (Amd1(-/-)) blastocysts at E3.5 arrested cell proliferation immediately after the onset of cell culture, and this arrest was rescued by the addition of spermidine. Chromosomal DNA breakage did not occur in Amd1(-/-) blastocysts at E3.5, as determined by TUNEL assay.
Conclusions:
These results indicate that AdoMetDC plays an essential role in embryonic development and that polyamines are required for cell proliferation in the embryo after E3.5.