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.
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 mouseAmd1 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.
Authors: Chenxu Shi; Timothy K Cooper; Diane E McCloskey; Adam B Glick; Lisa M Shantz; David J Feith Journal: Carcinogenesis Date: 2012-05-19 Impact factor: 4.944
Authors: Yoshihiko Ikeguchi; Xiaojing Wang; Diane E McCloskey; Catherine S Coleman; Paul Nelson; Guirong Hu; Lisa M Shantz; Anthony E Pegg Journal: Biochem J Date: 2004-08-01 Impact factor: 3.857
Authors: Alexander Heinick; Katja Urban; Stefan Roth; Danica Spies; Frank Nunes; Otto Phanstiel; Eva Liebau; Kai Lüersen Journal: FASEB J Date: 2009-09-17 Impact factor: 5.191
Authors: Lan Xiao; Jaladanki N Rao; Tongtong Zou; Lan Liu; Bernard S Marasa; Jie Chen; Douglas J Turner; Huiping Zhou; Myriam Gorospe; Jian-Ying Wang Journal: Mol Biol Cell Date: 2007-09-05 Impact factor: 4.138