Characterization of transgenic mice with overexpression of spermidine synthase

Chenxu Shi, Patricia A. Welsh, Suzanne Sass-Kuhn, Xiaojing Wang, Diane E. McCloskey, Anthony E. Pegg, David J. Feith

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

A composite cytomegalovirus-immediate early gene enhancer/chicken β-actin promoter (CAG) was utilized to generate transgenic mice that overexpress human spermidine synthase (SpdS) to determine the impact of elevated spermidine synthase activity on murine development and physiology. CAG-SpdS mice were viable and fertile and tissue SpdS activity was increased up to ninefold. This increased SpdS activity did not result in a dramatic elevation of spermidine or spermine levels but did lead to a 1.5- to 2-fold reduction in tissue spermine:spermidine ratio in heart, muscle and liver tissues with the highest levels of SpdS activity. This new mouse model enabled simultaneous overexpression of SpdS and other polyamine biosynthetic enzymes by combining transgenic animals. The combined overexpression of both SpdS and spermine synthase (SpmS) in CAG-SpdS/CAG-SpmS bitransgenic mice did not impair viability or lead to overt developmental abnormalities but instead normalized the elevated tissue spermine:spermidine ratios of CAG-SpmS mice. The CAG-SpdS mice were bred to MHC-Ado- MetDC mice with a >100-fold increase in cardiac S-adenosylmethionine decarboxylase (AdoMetDC) activity to determine if elevated dcAdoMet would facilitate greater spermidine accumulation in mice with SpdS overexpression. CAG-SpdS/MHC-AdoMetDC bitransgenic animals were produced at the expected frequency and exhibited cardiac polyamine levels comparable to MHCAdoMetDC littermates. Taken together these results indicate that SpdS levels are not rate limiting in vivo for polyamine biosynthesis and are unlikely to exert significant regulatory effects on cellular polyamine content and function.

Original languageEnglish (US)
Pages (from-to)495-505
Number of pages11
JournalAmino Acids
Volume42
Issue number2-3
DOIs
StatePublished - Feb 1 2012

Fingerprint

Spermidine Synthase
Transgenic Mice
Spermidine
Polyamines
Spermine
Adenosylmethionine Decarboxylase
Tissue
Spermine Synthase
Animals
Genetically Modified Animals
Immediate-Early Genes
Biosynthesis
Physiology

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Shi, C., Welsh, P. A., Sass-Kuhn, S., Wang, X., McCloskey, D. E., Pegg, A. E., & Feith, D. J. (2012). Characterization of transgenic mice with overexpression of spermidine synthase. Amino Acids, 42(2-3), 495-505. https://doi.org/10.1007/s00726-011-1028-6
Shi, Chenxu ; Welsh, Patricia A. ; Sass-Kuhn, Suzanne ; Wang, Xiaojing ; McCloskey, Diane E. ; Pegg, Anthony E. ; Feith, David J. / Characterization of transgenic mice with overexpression of spermidine synthase. In: Amino Acids. 2012 ; Vol. 42, No. 2-3. pp. 495-505.
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Shi, C, Welsh, PA, Sass-Kuhn, S, Wang, X, McCloskey, DE, Pegg, AE & Feith, DJ 2012, 'Characterization of transgenic mice with overexpression of spermidine synthase', Amino Acids, vol. 42, no. 2-3, pp. 495-505. https://doi.org/10.1007/s00726-011-1028-6

Characterization of transgenic mice with overexpression of spermidine synthase. / Shi, Chenxu; Welsh, Patricia A.; Sass-Kuhn, Suzanne; Wang, Xiaojing; McCloskey, Diane E.; Pegg, Anthony E.; Feith, David J.

In: Amino Acids, Vol. 42, No. 2-3, 01.02.2012, p. 495-505.

Research output: Contribution to journalArticle

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