JAX® Mice Strain Sleeps While Standing
JAX® NOTES Issue 504, Winter 2006
At the very moment when Jackson Laboratory biologist Peter Reifsnyder was in the doctor's office being diagnosed with sleep apnea, a sleep disorder that troubles roughly 12 million Americans, some animal technicians in one of the Laboratory's mouse rooms were curiously observing a very odd behavior by individuals of a mouse strain called New Zealand Obese (NZO/HlLtJ, 002105). The mice were standing vertically upright on their hind legs - while sleeping. When Reifsnyder himself observed this behavior, he immediately suspected that it was a kind of sleep apnea. The discovery of this unusual behavior in mice is a significant breakthrough because, until then, the only known animal model of sleep apnea was the English bulldog (Hendricks et al. 1987).
Although apparently rare in other animals, in humans, sleep apnea, clinically called obstructive sleep apnea (OSA), is as common as adult diabetes. It may affect people of any age and sex, but it is more prevalent in males, people who are overweight, and people who are over 40. Due to a general lack of awareness of the disease by health care professionals, the vast majority of people with sleep apnea are undiagnosed and untreated.
In Greek, the word apnea means "without breath." While sleeping, people with sleep apnea repeatedly stop breathing, wake up, and fall back asleep, sometimes several hundred times a night. As a result, they are exhausted the next day, and may nod off at work, at traffic signals, and while driving.
Sleep apnea is increasingly recognized as a risk factor for hypertension, cardiovascular disease, and metabolic syndrome, and it has been implicated in memory loss, obesity, impotence, and headaches.
Fortunately, sleep apnea can be treated. Treatments include sleeping in a semi-prone position, losing weight, wearing a pressurized mask that keeps the airway open during sleep, surgery to modify the airway, and a dental device that pulls the jaws forward.
Reifsnyder's sleep apnea and that of the NZO mice have different causes. Whereas Reifsnyder's apnea is due to his jaws being located farther back than normal, allowing his tongue to repeatedly interfere with breathing during his sleep, the NZO apnea is hypothesized to be due to airway compression by unusually large neck fat pads when the mice are prone. Researchers are testing this hypothesis by analyzing magnetic resonance images (MRIs) and the behaviors of some NZO mice temporarily housed in a sophisticated Comprehensive Cage Monitoring System (CCMS), which, among other things, assesses sleep patterns. The sleep-assessment component of the CCMS was developed in cooperation with the University of Pennsylvania's Dr. Allan Pack, a collaborator in The Jackson Laboratory's Center for New Mouse Models of Heart, Lung, Blood, and Sleep (HLBS) Disorders (featured in the last issue of JAX® NOTES). One of the goals of the HLBS Center is to identify and/or produce new mouse models of sleep disorders.
The discovery of the unusual sleep behavior of NZO mice prompted some Jackson Laboratory staff to examine other mouse strains for similar behavior. They soon discovered that two other strains of obese mice and two strains of lean mice exhibit fragmented sleep - though none of these strains were observed standing while sleeping.
Research indicates that the cause of sleep apnea is at least partly genetic. Identifying the alleles responsible for sleep disorders in mouse models could help researchers find the fundamental cause of and better treatments for sleep apnea. Comments Dr. Luanne Peters, Senior Staff Scientist at The Jackson Laboratory and principal investigator of the HLBS project: "For the first time, this gives us genetically defined mice in which we can start to look for the genes that cause this disorder. More research must correlate the mouse's sleepiness with blood chemistry to see if it mimics the blood-oxygen changes in the human disorder. But we have made progress toward monitoring blood oxygen levels reliably in the sleepy mice, and we'll be measuring them as soon as we can."
References
Cooke, Robert. 2006. Odd mice in apnea study. Newsday.com. Sep. 16.
JAX® NOTES. 2006. The Jackson Laboratory's Center for New Mouse Models of Heart, Lung, Blood, and Sleep Disorders. JAX® NOTES 503:1-3.
Hendricks JC, Kline LR, Kovalski RJ, O'Brien JA, Morrison AR, Pack AI. 1987. The English bulldog: a natural model of sleep-disordered breathing. J Appl Physiol 63:1344-50.
