TIGP (BIO)—Nile Rat (Arvicanthis niloticus) as a Model for Advancing Biomedical and Evolutionary Science

Abstract

The Nile grass rat (Arvicanthis niloticus), a murid rodent native to Africa, is gaining recognition as a valuable model in biomedical research, particularly for studies on type 2 diabetes, circadian rhythm disorders, and neurobehavioral conditions. Unlike traditional nocturnal rodent models, its diurnal activity and metabolic rhythms closely resemble those of humans, making it a promising candidate for translational research. Beyond its biomedical relevance, A. niloticus is one of the few murid species to have transitioned from a nocturnal to a diurnal lifestyle. This shift has been accompanied by distinct phenotypic changes, especially in the visual system, offering a unique opportunity to investigate the evolutionary adaptations associated with diurnality in mammals.

To support reproducible research, inbred lines are essential as they provide genetically uniform animals that reduce experimental variability. While numerous inbred strains have been established for nocturnal rodents such as mice and rats, none currently exist for diurnal murids like the Nile grass rat. To fill this gap, we initiated the first inbreeding program for a diurnal murid at NHRI through continuous sibling mating. A major challenge in this process is inbreeding depression, which typically occurs between generations F2 and F8 due to the expression of harmful recessive alleles. We have successfully advanced the colony to generation F15 with viable and fertile animals, representing a major step toward establishing the first inbred diurnal murid line for laboratory use.

Alongside the development of this inbred line, we have been investigating how the transition to diurnality has shaped the sensory systems of the Nile grass rat. Our research began with the study of its distinctive white eye-ring. Comparative analyses of diel activity and facial coloration across 540 rodent species revealed that the white eye-ring evolved independently multiple times in association with diurnal behavior. Behavioral experiments suggest this trait may function in visual species recognition.

We then examined whether the sensory evolution of A. niloticus reflects a tradeoff between vision and olfaction. Comparisons with its nocturnal relatives, Mus musculus and Rattus norvegicus, showed that the Nile grass rat has reduced several key odorant-sensing structures, including the turbinal bones, cribriform plate, and olfactory bulb. Genomic analysis of olfactory receptor genes revealed increased gene loss, reduced gene gain, lower expression levels, and relaxed selective constraints. These results support a sensory tradeoff hypothesis, in which enhanced visual capability has been accompanied by a decline in olfactory function.

Together, these findings underscore the Nile grass rat’s exceptional value as a dual-purpose model. It provides key insights into the evolution of sensory systems in response to diurnality and meets urgent needs in biomedical research. With the successful development of an inbred line, A. niloticus is now positioned to serve as a powerful and reproducible platform for advancing human-relevant science.

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