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Symptoms of restless leg syndrome observed in Btbd9 mutant mice, a potential model organism
Restless leg syndrome is a neurological disorder in which there is little knowledge of its origin and functioning pathway, despite its affect on 3-10% of the general population. Restless leg syndrome is characterized by uncomfortable sensations that generally arise in the legs, at night or during sleep, and lead to an irresistible urge to move. The disorder often results in sleep disturbances that cause daytime drowsiness as well as frustration and a decreased quality of life. Previous studies exemplify the genetic component of this disorder; one showed a family history in 60% of all restless leg syndrome cases and another revealed a high genetic component among twins.
Two recent genome-wide studies have found that mutations in the gene, BTBD9, are associated with a higher risk of restless leg syndrome. Using the results of the genome-wide studies, the authors of this paper have developed a BTBD9 gene mutant mouse that demonstrates very similar symptoms to those of restless leg syndrome in humans. The study found an increase in restlessness of the mutant mouse, based on its activity level, a characteristic that defines restless leg syndrome. Restless leg syndrome is also defined by uncomfortable sensations. To test for these sensations, the researchers looked for thermal sensory alterations in the mutant mice. The authors found a decreased response to heat during their resting time and no change during their active time. This suggests a circadian component in the sensory alterations of the mutant mice, similar to people with restless leg syndrome who are known to experience these uncomfortable sensations primarily during their resting time. Interestingly, the sensory alterations in the mutant mice were relieved when treated with ropinirole, a dopaminergic drug that is already used to treat human restless leg syndrome. Furthermore, a test on the mutant mouse’s sleep structure found increased awakeness during their rest time, just as those with restless leg syndrome are known to awaken more often during the night than the average person. All of these findings greatly parallel the symptoms associated with restless leg syndrome in humans. Therefore, the researchers think this BTBD9 gene mutant mouse may currently be the most ideal model organism to begin further research.
Two recent genome-wide studies have found that mutations in the gene, BTBD9, are associated with a higher risk of restless leg syndrome. Using the results of the genome-wide studies, the authors of this paper have developed a BTBD9 gene mutant mouse that demonstrates very similar symptoms to those of restless leg syndrome in humans. The study found an increase in restlessness of the mutant mouse, based on its activity level, a characteristic that defines restless leg syndrome. Restless leg syndrome is also defined by uncomfortable sensations. To test for these sensations, the researchers looked for thermal sensory alterations in the mutant mice. The authors found a decreased response to heat during their resting time and no change during their active time. This suggests a circadian component in the sensory alterations of the mutant mice, similar to people with restless leg syndrome who are known to experience these uncomfortable sensations primarily during their resting time. Interestingly, the sensory alterations in the mutant mice were relieved when treated with ropinirole, a dopaminergic drug that is already used to treat human restless leg syndrome. Furthermore, a test on the mutant mouse’s sleep structure found increased awakeness during their rest time, just as those with restless leg syndrome are known to awaken more often during the night than the average person. All of these findings greatly parallel the symptoms associated with restless leg syndrome in humans. Therefore, the researchers think this BTBD9 gene mutant mouse may currently be the most ideal model organism to begin further research.
References
DeAndrade, Mark P., et al. (2012). Motor restlessness, sleep disturbances, thermal sensory alterations and elevated serum iron levels in Btbd9 mutant mice. Human Molecular Genetics. 21(18), 3984-3992. Doi: 10.1093/hmg/dds221