Capitol News

A team of researchers at Michigan State University (MSU) has discovered a set of methods that enabled the first successful CRISPR-based genome editing in Nile grass rats. The study, published in BMC Biology, marks the first instance of genome editing in these diurnal rodents, which have sleep/awake patterns similar to humans. This similarity could be advantageous for preclinical or translational research.

Currently, preclinical research relies heavily on laboratory mice, nocturnal rodents active at night and asleep during the day. Diurnal and nocturnal mammals have evolved differently, including having distinct neural circuits and gene-regulatory networks.

“The differences between diurnal and nocturnal mammals present a significant translational flaw when applying the research findings obtained from mice to humans. Numerous therapeutic agents such as neuroprotectants proven effective in mouse or rat models of cerebral ischemia have failed in human clinical stroke trials, with mounting evidence suggesting the nocturnal and diurnal differences causing such failures,” said Lily Yan, co-author of the study and professor in MSU’s Department of Psychology.

Katrina Linning-Duffy and Jiaming Shi, also co-authors on the research, work in Yan's lab. Given the complex differences between diurnal and nocturnal animals, researchers believe a diurnal model is essential to understand genes' relationships with behaviors relevant to human health and disease.

The method developed includes a superovulation protocol yielding nearly 30 eggs per female. Protocols for in vitro embryo culture and manipulation were also developed alongside in vivo gene targeting using GONAD (Genome editing via Oviductal Nucleic Acids Delivery) methods.

The Nile grass rat colony at MSU is a unique resource established on campus since 1993 through joint efforts by the departments of Psychology and Integrative Biology and the Transgenic and Genome Editing Facility. Research projects involving Nile grass rats at MSU have been continuously funded for over 30 years. Animals from this colony have been shared with more than 20 research labs globally studying various topics including circadian rhythms, sleep, mood cognition, immune function, metabolic syndromes, and evolutionary biology.

“We hope that Nile grass rats will eventually become an alternative mammalian model to investigate genes’ roles in any biological processes where chronotype (diurnal vs. nocturnal) is a critical biological variable,” Yan said. “This study will be an essential first step towards that far-reaching goal.”

Co-authors on this research include Huirong Xie, program director of MSU's Transgenic and Genome Editing Facility; Katrina Linning-Duffy; Jiaming Shi; all members working within Yan's lab.