You may have wondered why some people seem to need less sleep. Is it in their genes? It turns out it’s likely. A number of so-called short sleeper genes, associated with a low need for sleep, have recently been identified through years of painstaking research and chance.
Now, researchers at the RIKEN Quantitative Biology Center (QBiC) have advanced sleep genetics research by developing a new method to monitor sleep cycles in mice. The Snappy Sleep Stager is a non-invasive, automated sleep cycle monitoring system based on mouse breathing or respiration. Compared to other monitoring systems that require surgical implants or many hours of human intervention, the Snappy Sleep Stager is easy to use and allows more mice to be studied during an experiment. By combining it with a new system for developing near-perfect knockout mice, they have identified a new short sleeper gene, Nr3a.
“The problem with sleep studies is that they are technically difficult and expensive, which limits the number of mice that can be studied,” says Hiroki Ueda of RIKEN QBiC, who led the research published in Cell Reports.
The low cost and ease of use of the Snappy Sleep Stager allowed researchers to accurately test a new mouse genetic modification system, the next-generation triple CRISPR method.
“The biggest advantage of our method is its efficiency,” says Kenta Sumiyama, co-first author of RIKEN QBiC. “Our goal was an efficiency of more than 90% and we achieved that. Our goal now is to be able to completely switch off any desired gene.”
The efficiency also benefits the mice, Sumiyama continues: “The new system allows us to analyze phenotypes directly without producing more than one generation of mice. There is a big difference in the number of mice used. Maybe ten times fewer mice are needed.” Get what’s called a bi-allelic knockout mouse. These mice, which are missing both copies of a “knocked out” gene, can provide a deeper understanding of the missing gene.
Sumiyama says he wasn’t surprised by the improved efficiency and that the research went fairly smoothly, but he admits the bigger challenge is making highly efficient “knock-in” animals, saying, “Inserting a Gens is a lot harder than removing it.”
According to Sumiyama, “You can target any disease caused by a genetic mutation with the triple CRISPR method.” In the current research, the scientists found that the Nr3a gene, a member of the NMDA receptor family, is a short sleeper gene. “The implications are far-reaching,” says Genshiro A. Sunagawa of the RIKEN Center for Developmental Biology, a first author on the publication. “As the NMDA receptor is associated with schizophrenia, Alzheimer’s disease and depression, which are known to involve sleep disorders.”
In addition to these disorders, sleep cycle disorders are known to be associated with many health problems. Sunagawa says, “It was known that sleep could be staged by monitoring breathing,” but existing technology for monitoring sleep stages usually requires direct manipulation of the subject or a very small chamber to monitor breathing.
“The beauty of the SSS is that it can be used in a larger enclosure that allows a mouse to live a normal lifespan. With our system, changes in sleep could be observed as a mouse ages. This is a big advantage over other systems,” says Sunagawa. He continues: “It could even be used to monitor babies or sleepy drivers in cars. Those would be good applications.”
“SSS can also be used in combination with MRI, which is another major benefit over other systems.” Sunagawa concludes, “We haven’t optimized the system to detect REM sleep, but it’s something besides MRI studies, which we are working on now.”
Materials provided by RIKEN. Note: Content can be edited for style and length.