Submitted on July 19, 2006
Accepted on August 7, 2007
Polyamine Homeostasis in Arginase Knockout Mice
Joshua LaCroix Deignan1, Justin Livesay2, L.M. Shantz3, Anthony E Pegg4, William O'Brien5, Ramaswamy Iyer1, Stephen Cederbaum6, and Wayne Grody7*
1 Pathology, UCLA, Los Angeles, California, United States; The Mental Retardation Research Center, UCLA, Los Angeles, California, United States
2 The Mental Retardation Research Center, UCLA, Los Angeles, California, United States
3 Penn St Univ College Med, United States
4 Hershey Medical Center, Pennsylvania State University, Hershey, Pennsylvania, United States
5 Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
6 Psychiatry, UCLA, Los Angeles, California, United States; Pediatrics, UCLA, Los Angeles, California, United States; The Mental Retardation Research Center, UCLA, Los Angeles, California, United States; Human Genetics, UCLA, Los Angeles, California, United States
7 Pathology, UCLA, Los Angeles, California, United States; The Mental Retardation Research Center, UCLA, Los Angeles, California, United States; Pediatrics, UCLA, Los Angeles, California, United States; Human Genetics, UCLA, Los Angeles, California, United States
* To whom correspondence should be addressed. E-mail: wgrody{at}mednet.ucla.edu.
The role of ornithine decarboxylase (ODC) in polyamine metabolism has long been established, but the exact source of ornithine has always been unclear. The arginase enzymes are capable of producing ornithine for the production of polyamines and may hold important regulatory functions in the maintenance of this pathway. Utilizing our unique set of arginase single and double knockout mice, we analyzed polyamine levels in the livers, brains, kidneys, and small intestines at two weeks of age, the latest timepoint at which all of them are still alive, in order to determine if tissue polyamine levels were altered in response to a disruption of arginase I and II enzymatic activity. While putrescine was minimally increased in the liver and kidneys from the AII knockout mice, spermidine and spermine were maintained. ODC activity was not greatly altered in the knockout animals and did not correlate with the fluctuations in putrescine. mRNA levels of OAT, AZ1, and SSAT were also measured and only minor alterations were seen, most notably an increase in OAT expression seen in the liver of arginase I knockout and double knockout mice. It appears that putrescine catabolism may be affected in the liver when AI is disrupted and ornithine levels are highly reduced. These results suggest that endogenous arginase-derived ornithine may not directly contribute to polyamine homeostasis in mice. Alternate sources such as diet may provide sufficient polyamines for maintenance in mammalian tissues.
