Characterization of transgenic mice with widespread overexpression of spermine synthase

Yoshihiko Ikeguchi, Xiaojing Wang, Diane E. McCloskey, Catherine S. Coleman, Paul Nelson, Guirong Hu, Lisa M. Shantz, Anthony E. Pegg

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

A widespread increase in SpmS (spermine synthase) activity has been produced in transgenic mice using a construct in which the human SpmS cDNA was placed under the control of a composite CMV-IE (cytomegalovirus immediate early gene) enhancer-chicken β-actin promoter. Four separate founder CAG/SpmS mice were studied. Transgenic expression of SpmS was found in all of the tissues examined, but the relative SpmS activities varied widely according to the founder animal and the tissue studied. Very large increases in SpmS activity were seen in many tissues. SpdS (spermidine synthase) activity was not affected. Although there was a statistically significant decline in spermidine content and increase in spermine, the alterations were small compared with the increase in SpmS activity. These results provide strong support for the concept that the levels of the higher polyamines spermidine and spermine are not determined only by the relative activities of the two aminopropyltransferases. Other factors such as availability of the aminopropyl donor substrate decarboxylated S-adenosylmethionine and possibly degradation or excretion must also influence the spermidine/spermine ratio. No deleterious effects of SpmS overexpression were seen. The mice had normal growth, fertility and behaviour up to the age of 12 months. However, breeding the CAG/SpmS mice with MHC (α-myosin heavy chain)/AdoMetDC (S-adenosylmethionine decarboxylase) mice, which have a large increase in S-adenosylmethionine decarboxylase expression in heart, was lethal. In contrast, breeding the CAG/SpmS mice with MHC/ODC (L-ornithine decarboxylase) mice, which have a large increase in cardiac ornithine decarboxylase expression, had a protective effect in preventing the small decrease in viability of the MHC/ODC mice.

Original languageEnglish (US)
Pages (from-to)701-707
Number of pages7
JournalBiochemical Journal
Volume381
Issue number3
DOIs
StatePublished - Aug 1 2004

Fingerprint

Spermine Synthase
Spermidine
Spermine
Myosin Heavy Chains
Spermidine Synthase
Adenosylmethionine Decarboxylase
Transgenic Mice
Ornithine Decarboxylase
Tissue
Polyamines
Actins
Animals
Complementary DNA
Breeding
Genes
Availability
Degradation
Composite materials
Substrates
Immediate-Early Genes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ikeguchi, Y., Wang, X., McCloskey, D. E., Coleman, C. S., Nelson, P., Hu, G., ... Pegg, A. E. (2004). Characterization of transgenic mice with widespread overexpression of spermine synthase. Biochemical Journal, 381(3), 701-707. https://doi.org/10.1042/BJ20040419
Ikeguchi, Yoshihiko ; Wang, Xiaojing ; McCloskey, Diane E. ; Coleman, Catherine S. ; Nelson, Paul ; Hu, Guirong ; Shantz, Lisa M. ; Pegg, Anthony E. / Characterization of transgenic mice with widespread overexpression of spermine synthase. In: Biochemical Journal. 2004 ; Vol. 381, No. 3. pp. 701-707.
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Ikeguchi, Y, Wang, X, McCloskey, DE, Coleman, CS, Nelson, P, Hu, G, Shantz, LM & Pegg, AE 2004, 'Characterization of transgenic mice with widespread overexpression of spermine synthase', Biochemical Journal, vol. 381, no. 3, pp. 701-707. https://doi.org/10.1042/BJ20040419

Characterization of transgenic mice with widespread overexpression of spermine synthase. / Ikeguchi, Yoshihiko; Wang, Xiaojing; McCloskey, Diane E.; Coleman, Catherine S.; Nelson, Paul; Hu, Guirong; Shantz, Lisa M.; Pegg, Anthony E.

In: Biochemical Journal, Vol. 381, No. 3, 01.08.2004, p. 701-707.

Research output: Contribution to journalArticle

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Ikeguchi Y, Wang X, McCloskey DE, Coleman CS, Nelson P, Hu G et al. Characterization of transgenic mice with widespread overexpression of spermine synthase. Biochemical Journal. 2004 Aug 1;381(3):701-707. https://doi.org/10.1042/BJ20040419