Sleep and wakefulness in c-fos and fos B gene knockout mice

G-protein coupled receptor (GPCR) stimulation has been implicated in the re gulation of sleep. Upon stimulation of a GPCR an intracellular cascade invo lving second and third messengers is initiated. The latter include the fos- family of immediate early genes (IEGs). Although there is considerable evid ence indicating that IEGs are expressed in response to sleep, the effects o f their deletion on sleep is not known. The present study examined sleep-wa kefulness in mice lacking the c-fos or fos B genes. Null c-fos mice compare d to their wildtype (WT) and heterozygote (het) siblings had more wakefulne ss and less slow wave sleep (SWS); REM sleep was not affected. The null c-f os mice also had increased delta activity (0.3-4 Hz). In contrast, the null and heterozygote fos B mice had less REM sleep, but the time spent in SWS or wakefulness was not different from their wild-type (WT) siblings. in the null c-fos mice, the increased wakefulness and the reduction in SWS could not be due to a systemic alteration in temperature since the core temperatu re was similar in all mice. By demonstrating that these IEGs are involved i n sleep, we suggest that the deletion of specific genes, even within a fami ly of genes, can have a specific effect on sleep. (C) 2000 Elsevier Science B.V. All rights reserved.