A team of researchers from Michigan State University has discovered a series of methods that enabled the first successful CRISPR-based genome editing in Nile grass rats.
The study, published in BMC Biologyis the first to successfully edit the genomes of Nile grass rats. As diurnal rodents, Nile grass rats have similar sleep/wake patterns to humans, which could be beneficial in preclinical or translational research.
Currently, preclinical research relies heavily on laboratory mice, which are nocturnal rodents that are active at night and sleep during the day. With these different sleep patterns, diurnal and nocturnal mammals have evolved differently, including having distinct wiring of neural circuits and gene regulatory networks.
“The differences between diurnal and nocturnal animals represent a significant translational error when applying the research results obtained from mice to humans. Numerous therapeutic agents such as neuroprotectants that have proven effective in mouse or rat models of cerebral ischemia have failed in human stroke clinical trials, with increasing evidence that nocturnal and diurnal differences drive 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 of the study, work in Yan’s Lab.
Because the differences between diurnal and nocturnal animals are complex, the researchers believe that a diurnal model is essential to disentangle the relationship between genes and behaviors relevant to human health and disease.
The developed method includes a superovulation protocol that can yield almost 30 eggs per female. They also developed protocols for in vitro – outside the body – embryo culture and manipulation and in vivo – in the living body – gene targeting using GONAD, or Genome editing via Oviductal Nucleic Acids Delivery, methods.
The Nile Grass Rat colony is a unique resource available at MSU. Through the joint efforts of the Departments of Psychology and Integrative Biology and the Transgenic and Genome Editing Facility, a colony of Nile grass rats was established on campus in 1993.
Research projects at MSU involving Nile grass rats have been continuously funded for more than 30 years. Animals from the MSU grass rat colony have been shared with more than two dozen research labs in the US, Canada, Belgium, China and Japan studying topics such as circadian rhythms and sleep, mood and cognition, immune function, metabolic syndromes and evolutionary biology.
Huirong Xie is program director of MSU’s Transgenic and Genome Editing Facility.
“We hope that Nile grass rats will eventually become an alternative mammalian model to investigate the role of genes in biological processes, especially in which chronotype (diurnal versus nocturnal) is a critical biological variable,” Yan said. “This study will be an essential first step toward the far-reaching goal.”
Co-authors of the study are Huirong Xie, program director of MSU Transgenic and Genome Editing Facility; Katrina Linning-Duffy and Jiaming Shi, who work in Yan’s Lab.
