Genetic manipulation of polyamine catabolism in rodents.
Activation of polyamine catabolism through the overexpression of spermidine/spermine N1-acetyltransferase (SSAT) in transgenic rodents does not only lead to distorted tissue polyamine homeostasis, manifested as striking accumulation of putrescine, appearance N1-acetylspermidine and reduction of tissue spermidine and/or spermine pools, but likewise creates striking phenotypic changes. The latter include loss of hair, lipoatrophy and female infertility. Forced expression of SSAT modulates skin, prostate and intestinal carcinogenesis, induces acute pancreatitis and blocks early liver regeneration. Although many of these features are directly attributable to altered tissue polyamine pools, some of them are more likely related to the greatly accelerated flux of the polyamines caused by activated catabolism and compensatorily enhanced biosynthesis.
Jänne
Juhani
J
Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio, Finland. Juhani.Janne@uku.fi
Alhonen
Leena
L
Pietilä
Marko
M
Keinänen
Tuomo A
TA
Uimari
Anne
A
Hyvönen
Mervi T
MT
Pirinen
Eija
E
Järvinen
Aki
A
D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D005786:Gene Expression Regulation / Q000235:genetics; D018014:Gene Transfer Techniques; D020022:Genetic Predisposition to Disease; D051379:Mice; D009369:Neoplasms / Q000235:genetics*; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D011073:Polyamines; D000099228:Diamine N-Acetyltransferase