Use of (Gyro) Gy and Spermine Synthase Transgenic Mice to Study Functions of Spermine
The polyamines putrescine, spermidine, and spermine are essential for mammalian cell growth, differentiation, and cell death and have important physiological roles in all tissues. Many of the properties of polyamines that can be demonstrated in vitro are common to all three molecules with differences only in potency. Loss of any of the enzymes needed to make either putrescine or spermidine (which also prevent the production of spermine) is lethal, but male mice lacking spermine synthase (SpmS) due to a deletion of part of the X chromosome are viable on the B6C3H background. These mice are termed Gyro (Gy) due to their circling behavior. They have a variety of abnormalities including deafness, neurological problems, small size, and a tendency to early death. They can therefore be used to evaluate the physiological function(s) uniquely provided by spermine. They also provide a potential animal model for Snyder-Robinson syndrome (SRS), a rare human inherited disease due to a loss of SpmS activity. An essential control in experiments using Gy mice is to demonstrate that the abnormal phenotypes exhibited by these mice are abolished by providing replacement spermine and this can be accomplished by breeding with CAG-SMS mice that express SpmS from a ubiquitous promoter. Techniques for identifying, characterizing, and using these mouse strains and limitations of this approach are described in this chapter.
Key wordsSpermine Spermine synthase Gy mice CAG-SMS mice
This work was supported by grant 3R01GM026290-29S1 from the NIH using funds from the NIH Recovery Act.
- 3.Korhonen V-P, Niranen K, Halmekyto M, Pietilä M, Diegelman P, Parkkinen JJ, Eloranta T, Porter CW, Alhonen L, Jänne J (2001) Spermine deficiency resulting from targeted disruption of the spermine synthase gene in embryonic stem cells leads to enhanced sensitivity to antiproliferative drugs. Mol Pharmacol 59:231–238PubMedGoogle Scholar
- 22.de Alencastro G, McCloskey DE, Kliemann SE, Maranduba CM, Pegg AE, Wang X, Bertola DR, Schwartz CE, Passos-Bueno MR, Sertie AL (2008) New SMS mutation leads to a striking reduction in spermine synthase protein function and a severe form of Snyder-Robinson X-linked recessive mental retardation syndrome. J Med Genet 45:539–543PubMedCrossRefGoogle Scholar
- 23.Becerra-Solano LE, Butler J, Castañeda-Cisneros G, McCloskey DE, Wang X, Pegg AE, Schwartz CE, Sánchez-Corona J, Garcia-Ortiz JE (2009) A missense mutation, p.V132G, in the X-linked spermine synthase gene (SMS) causes Snyder-Robinson syndrome. Am J Med Genet A 149A:328–335PubMedCrossRefGoogle Scholar
- 24.Schwartz C, Pegg AE (2010) Methods in molecular biology. In: Pegg AE, Casero RA Jr (eds) Polyamine protocols. Humana Press, TotowaGoogle Scholar
- 26.Kabra PM, Lee HK, Lubich WP, Marton LW (1986) Solid-phase extraction and determination of dansyl derivatives of unconjugated and acetylated polyamines by reversed-phase liquid chromatography; improved separation systems for polyamines in cerebrospinal fluid, urine and tissue. J Chromatogr Biomed Appl 380:19–32CrossRefGoogle Scholar
- 27.Häkkinen MR (2010) Polyamine analysis by LC-MS. In: Pegg AE, Casero RA Jr (eds) Methods in molecular biology. Polyamine protocols. Totowa, Humana PressGoogle Scholar
- 29.Schwartz CE, Stevenson RE, Wang X, Pegg AE (2010) Spermine synthase deficiency resulting in X-linked intellectual disability (Snyder-Robinson syndrome). In: Pegg AE, Casero RA Jr (eds) Methods in molecular biology. Polyamine protocols. Totowa, Humana PressGoogle Scholar