Tyr-Uroguanylin (mouse, rat)

As 2020 is "The Year of the Rat" in the Chinese astrological calendar, it seems an appropriate time to consider whether we should bring back the laboratory rat to front-and-center in research on the basic biology of mammalian aging. Beginning in the 1970s, aging research with rats became common, peaking in 1992 but then declined dramatically by 2018 as the mouse became preeminent. The purpose of this review is to highlight some of the historical contributions as well as current advantages of the rat as a mammalian model of human aging, because we suspect at least a generation of researchers is no longer aware of this history or these advantages. Herein, we compare and contrast the mouse and rat in the context of several biological domains relevant to their use as appropriate models of aging: phylogeny/domestication, longevity interventions, pathology/physiology, and behavior/cognition. It is not the goal of this review to give a complete characterization of the differences between mice and rats, but to provide important examples of why using rats as well as mice is important to advance our understanding of the biology of aging.

Mice and rats are the most commonly used vertebrate model organisms in biomedical research. The availability of a reference genome in both animals combined with the deep sequencing of several doze of popular inbred lines also provides rich sequence variation data in these species. In some cases, such sequence variants can be linked directly to a distinctive phenotype. In previous work, we created the mouse and rat online searchable databases ("Mousepost" and "Ratpost") where small variant information for protein coding transcripts in mouse and rat inbred strains can be easily retrieved at the amino acid level. These tools are directly useful in forward genetics strategies or as a repository of existing sequence variations. Here, we perform a comparison between the "Mousepost" and "Ratpost" databases and we couple these two tools to a database of human sequence variants ClinVar. We investigated the level of redundancy and complementarity of known variants in protein coding transcripts and found that the large majority of variants is species-specific. However, a small set of positions is conserved in an inbred line between both species. We conclude that both databases are highly complementary, but this may change with further sequencing efforts in both species.