Deficient Sleep in Mouse Models of Fragile X Syndrome.

In patients with fragile X syndrome (FXS), sleep problems are commonly observed but are not well characterized. In animal models of FXS ( and knockout (KO)/ heterozygote) circadian rhythmicity is affected, but sleep has not been examined. We used a home-cage monitoring system to assess total sleep time in both light and dark phases in KO mice at different developmental stages. KOs at P21 do not differ from controls, but genotype × phase interactions in both adult (P70 and P180) groups are statistically significant indicating that sleep in KOs is reduced selectively in the light phase compared to controls. Our results show the emergence of abnormal sleep in KOs during the later stages of brain maturation. Treatment of adult KO mice with a GABA agonist, R-baclofen, did not restore sleep duration in the light phase. In adult (P70) KO heterozygote animals, total sleep time was further reduced, once again in the light phase. Our data highlight the importance of the fragile X genes ( and ) in sleep physiology and confirm the utility of these mouse models in enhancing our understanding of sleep disorders in FXS.