Oncotarget

Research Papers:

The rabbit as an orthologous small animal model for APOBEC3A oncogenesis

Hélène C. Laude, Vincent Caval, Mohamed S. Bouzidi, Xiongxiong Li, Florence Jamet, Michel Henry, Rodolphe Suspène, Simon Wain-Hobson and Jean-Pierre Vartanian _

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Oncotarget. 2018; 9:27809-27822. https://doi.org/10.18632/oncotarget.25593

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Abstract

Hélène C. Laude1, Vincent Caval1, Mohamed S. Bouzidi1, Xiongxiong Li1,2, Florence Jamet1, Michel Henry1, Rodolphe Suspène1, Simon Wain-Hobson1 and Jean-Pierre Vartanian1

1Molecular Retrovirology Unit, Institut Pasteur, CNRS UMR 3569, France

2Lanzhou Institute of Biological Products Co., Ltd (LIBP), subsidiary company of China National Biotec Group Company Limited (CNBG), Lanzhou 730046, China

Correspondence to:

Jean-Pierre Vartanian, email: jean-pierre.vartanian@pasteur.fr

Keywords: rabbit; animal model; APOBEC3A; cytidine deaminase; cancer

Received: March 15, 2018     Accepted: May 24, 2018     Published: June 12, 2018

ABSTRACT

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 APOBEC3 locus is conserved in mammals, it encodes from 1–7 genes. APOBEC3A is conserved in most mammals, although absent in pigs, cats and throughout Rodentia whereas APOBEC3B is restricted to the Primate order. Here we show that the rabbit APOBEC3 locus encodes two genes of which APOBEC3A 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 APOBEC3A gene is widely expressed in rabbit tissues, unlike human APOBEC3A. These data demonstrate that rabbit could be used as a small animal model for studying APOBEC3 driven oncogenesis.


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