Spermine synthesis is required for normal viability, growth, and fertility in the mouse

Xiaojing Wang, Yoshihiko Ikeguchi, Diane E. McCloskey, Paul Nelson, Anthony E. Pegg

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Abstract

Spermidine is essential for viability in eukaryotes but the importance of the longer polyamine spermine has not been established. Spermine is formed from spermidine by the action of spermime synthase, an aminopropyltransferase, whose gene (SpmS) is located on the X chromosome. Deletion of part of the X chromosome that include SpmS in Gy mice leads to a striking phenotype in affected males that includes altered phosphate metabolism and symptoms of hypophosphatemic rickets, circling behavior, hyperactivity, head shaking, inner ear abnormalities, deafness, sterility, a profound post-natal growth retardation, and a propensity to sudden death. It was not clear to what extent these alterations were due to the loss of spermine synthase activity, since this chromosomal deletion extends well beyond the SpmS gene and includes at least one other gene termed Phex. We have bred the Gy carrier female mice with transgenic mice (CAG/SpmS mice) that express spermine synthase from the ubiquitous CAG promoter. The resulting Gy-CAG/SpmS mice had extremely high levels of spermine synthase and contained spermine in all tissues examined. These mice had a normal life span and fertility and a normal growth rate except for a reduction in body weight due to a loss of bone mass that was consistent with the observation that the derangement in phosphate metabolism is due to the loss of the Phex gene and was not restored. These results show that spermine synthesis is needed for normal growth, viability, and fertility in male mice and that regulation of spermine synthase content is not required.

Original languageEnglish (US)
Pages (from-to)51370-51375
Number of pages6
JournalJournal of Biological Chemistry
Volume279
Issue number49
DOIs
Publication statusPublished - Dec 3 2004

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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