title: Characterization of transgenic mice with widespread overexpression of spermine synthase.
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 beta-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 (alpha-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.
authors.affiliation: Department of Cellular and Molecular Physiology, The Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine. P.O. Box 850, Hershey, PA 17033, USA.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ikeguchi
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.forename: Diane E
authors.initials: DE
authors.lastname: McCloskey
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Coleman
authors.forename: Paul
authors.initials: P
authors.lastname: Nelson
authors.forename: Guirong
authors.initials: G
authors.lastname: Hu
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Shantz
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Pegg
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry; D003433:Crosses, Genetic; D003587:Cytomegalovirus / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D007668:Kidney / Q000737:chemistry / Q000201:enzymology; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology; D009928:Organ Specificity; D010053:Ovary / Q000737:chemistry / Q000201:enzymology; D010802:Phylogeny; D011073:Polyamines / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013097:Spermine Synthase / Q000235:genetics* / Q000378:metabolism; D013737:Testis / Q000737:chemistry / Q000201:enzymology
chemical_list: D011073:Polyamines; D011994:Recombinant Proteins; D013097:Spermine Synthase