Key result
Rabbits lack the calponin 2 gene and miss 843 human protein-coding genes compared to mice.
Why the study?
Selecting suitable animal models for human biology and disease studies requires consideration of whole-genome protein conservation, as rabbits lack certain human proteins like calponin 2 despite closer phylogenetic relation to humans than mice.
Rabbit models lacking calponin 2 may limit translational relevance; leaves open optimal species selection for human cardiovascular protein studies.
While the rapid development of CRISPR/CAS9 technology has allowed for readily performing site-specific genomic editing in non-rodent species, an emerging challenge is to select the most suitable species to generate animal models for the study of human biology and diseases. Improving CRISPR/CAS9 methodology for more effective and precise editing in the rabbit genome to replicate human disease is an active area of biomedical research. Although rabbits are more closely related to humans than mice (based on DNA sequence analysis), our whole-genome protein database search revealed that rabbits have more missing human protein sequences than mice. Hence, precisely replicating human diseases in rabbits requires further consideration, especially in studies involving essential functions of the missing proteins. For example, rabbits lack calponin 2, an actin-associated cytoskeletal protein that is important in the pathogenesis of inflammatory arthritis, atherosclerosis, and calcific aortic valve disease. The justification of using rabbits as models for human biomedical research is based on their larger size and their closer phylogenetic distance to humans (based on sequence similarity of conserved genes), but this may be misleading. Our findings, which consider whole-genome protein profiling together with actual protein expressions, serve as a warning to the scientific community to consider overall conservation as well as the conservation of specific proteins when choosing an animal model to study a particular aspect of human biology prior to investing in genetic engineering.
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Plazyo et al. (2020) studied this question. Rabbit animal model vs. Mouse animal model was evaluated on Presence of calponin 2 gene and protein. Whole-genome protein profiling and Western blotting revealed that rabbits lack the calponin 2 gene and have 843 missing human protein coding genes compared to 652 in mice.
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