The rabbit as an orthologous small animal model for APOBEC3A oncogenesis.

APOBEC3 are cytidine deaminases that convert cytidine to uridine residues. APOBEC3A and APOBEC3B enzymes able to target genomic DNA are involved in oncogenesis of a sizeable proportion of human cancers. While the locus is conserved in mammals, it encodes from 1-7 genes. is conserved in most mammals, although absent in pigs, cats and throughout whereas is restricted to the order. Here we show that the rabbit locus encodes two genes of which enzyme is strictly orthologous to human APOBEC3A. The rabbit enzyme is expressed in the nucleus and the cytoplasm, it can deaminate cytidine, 5-methcytidine residues, nuclear DNA and induce double-strand DNA breaks. The rabbit APOBEC3A enzyme is negatively regulated by the rabbit TRIB3 pseudokinase protein which is guardian of genome integrity, just like its human counterpart. This indicates that the APOBEC3A/TRIB3 pair is conserved over approximately 100 million years. The rabbit gene is widely expressed in rabbit tissues, unlike human . These data demonstrate that rabbit could be used as a small animal model for studying APOBEC3 driven oncogenesis.