The rabbit as an animal model to study innate immunity genes: Is it better than mice?

Abstract

The European rabbit (Oryctolagus cuniculus) was the first animal model used to understand human diseases like rabies and syphilis. Nowadays, the rabbit is still used to study several human infectious diseases like syphilis, HIV and papillomavirus. However, due to several mainly practical reasons, it has been replaced as an animal model by mice (Mus musculus). The rabbit and mouse share a recent common ancestor and are classified in the superorder Glires which arose at approximately 82 million years ago (mya). These species diverged from the Primates’ ancestor at around 92 million years ago and, as such, one expects the rabbit-human and mouse-human genetic distances to be very similar. To evaluate this hypothesis, we developed a set of tools for automatic data extraction, sequence alignment and similarity study, and a web application for visualization of the resulting data. We aligned and calculated the genetic distances for 2793 innate immune system genes from human, rabbit and mouse using sequences available in the NCBI database. The obtained results show that the rabbit-human genetic distance is lower than the mouse-human genetic distance for 88% of these genes. Furthermore, when we considered only genes with a difference in genetic distance higher than 0.05, this figure increase to 93%. These results can be explained by the increase of the mutation rates in the mouse lineage suggested by some authors and clearly show that, at least looking to the genetic distance to human genes, the European rabbit is a better model to study innate immune system genes than the mouse.