Polyamines are small linear cations derived from amino acids, involved in cell proliferation and differentiation and found in nearly all organisms. The more relevant polyamines are putrescine, spermidine, and spermine, and their roles are based on their ability to bind to biomolecules, importantly to nucleic acids.

The cellular levels of polyamines are subject to complex control. The rate limiting-step in the biosynthetic pathway of polyamines is ornithine decarboxylase (ODC), an enzyme regulated by the antizymes (AZ). In the presence of high levels of polyamines, this family of proteins drives ODC to ubiquitin-independent proteasomal degradation.

The activity of AZ is regulated at the translational level, by a mechanism of frameshift mediated by polyamines and at the post-translational level, by the inhibitor of antizyme (Azin1), a protein with high homology to ODC, and highly expressed in normal and neoplastic tissues.

The sequencing of the human and murine genomes unveiled the existence of multiple ODC paralogues with unknown functions such as ODCp. The functional analysis of mouse ODCp by Lopez-Contreras et al. (2006) showed that Odcp reverted Odc inhibition mediated by antizyme and revealed evidence of an interaction between Odcp and antizymes.

The nomenclature of the Odcp gene was replaced by Azin2 thereafter.

1. Acquisition and development of Azin2 knock-out mice. The Eucomm program is currently developing a conditional knock-out mouse for Azin2 linked to a LacZ reporter, which is currently at the chimera phase and can be used as a conditional knock-out mediated by Cre-recombinase.
2. Study of new expression patterns of Azin2 in mouse tissues. Although the high levels of Azin2 expression in brain and testis is widely known, we will search expression in other tissues where the total expression is not high, but potentially important at the single cell level. This study will be carried out by histochemical detection of LacZ reporter gene.
3. Study of the resulting phenotype associated with germ-line and conditional loss of Azin2. We will study the Azin2 expression by Xgal histochemistry in different mouse tissues
4. Molecular and biochemical analysis of the Azin2 deficient phenotype. We will study the polyamine levels and expression of polyamine related genes in the relevant tissues. The changes in expression of other loci will be studied by expression microarrays and in case it¿s advisable we will search changes in genome stability by genomic arrays.
5. Crossing of Azin2 deficient mice onto pathology predisposed mouse models. The involvement of polyamines in cancer is widely known and therefore we will cross Azin2 deficient mice onto cancer predisposed mouse models such as Min mice (intestinal adenomes) in order to search for changes in the tumour phenotype.