Spermine synthesis is required for normal viability, growth, and fertility in the mouse.
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 spermine 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 postnatal 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.
Wang
Xiaojing
X
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Ikeguchi
Yoshihiko
Y
McCloskey
Diane E
DE
Nelson
Paul
P
Pegg
Anthony E
AE
D000367:Age Factors; D000818:Animals; D001835:Body Weight; D002851:Chromatography, High Pressure Liquid; D002872:Chromosome Deletion; D003433:Crosses, Genetic; D005260:Female; D005298:Fertility / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D010710:Phosphates / Q000737:chemistry / Q000378:metabolism; D011073:Polyamines / Q000737:chemistry; D011401:Promoter Regions, Genetic; D013096:Spermine / Q000096:biosynthesis / Q000502:physiology*; D013097:Spermine Synthase / Q000096:biosynthesis / Q000235:genetics*; D013737:Testis / Q000473:pathology; D013997:Time Factors; D019076:Transgenes; D014960:X Chromosome / Q000648:ultrastructure
D010710:Phosphates; D011073:Polyamines; D013096:Spermine; D013097:Spermine Synthase