Abstract
The gene Disrupted in Schizophrenia-1 (DISC1) is linked to a range of psychiatric disorders. Two recent transgenic studies suggest DISC1 is also involved in homeostatic sleep regulation. Several strains of inbred mice commonly used for genome manipulation experiments, including several Swiss and likely all 129 substrains, carry a natural deletion mutation of Disc1. This constitutes a potential confound for studying sleep in genetically modified mice. Since disturbed sleep can also influence psychiatric and neurodegenerative disease models, this putative confound might affect a wide range of studies in several fields. Therefore, we asked to what extent the natural Disc1 deletion affects sleep. To this end, we first compared sleep and electroencephalogram (EEG) phenotypes of 129S4 mice carrying the Disc1 deletion and C57BL/6N mice carrying the full-length version. We then bred Disc1 from C57BL/6N into the 129S4 background, resulting in S4-Disc1 mice. The differences between 129S4 and C57BL/6N were not detected in the 129S4 to S4-Disc1 comparison. We conclude that the mutation has no effect on the measured sleep and EEG characteristics. Thus, it is unlikely the widespread Disc1 deletion has led to spurious results in previous sleep studies or that it alters sleep in mouse models of psychiatric or neurodegenerative diseases.
Highlights
Many psychiatric disorders, including schizophrenia, major depression, and bipolar disorder, are accompanied by pronounced sleep abnormalities[1, 2]
Vigilance states can be classified into wake, rapid eye movement sleep (REM) and non-rapid eye movement sleep (NREM)
Group means with standard deviations were 45.5 ± 1.8% wake, 49.0 ± 1.7% NREM, 5.5 ± 0.3% REM for S4 and 42.2 ± 1.1% wake, 53.6 ± 1.2% NREM, 4.2 ± 0.2% REM for B6N
Summary
Many psychiatric disorders, including schizophrenia, major depression, and bipolar disorder, are accompanied by pronounced sleep abnormalities[1, 2]. In contrast to most inbred mouse strains such as C57BL/6, several strains including “Swiss” strains (e.g. FVB, SJL, SWR), and all 129 substrains naturally carry a 25 base pair deletion mutation in exon 6 of Disc[113–15] Many of these strains have been widely used for genome manipulation techniques. Considering the above mentioned reports of altered sleep in human DISC1 expressing transgenic flies and mice and that the mouse Disc[1] deletion creates physiological changes, we wondered if the Disc[1] deletion would affect sleep This is important both for the quest of understanding links between sleep and psychiatric disease and to determine if it creates a potential confound for a large number of existing studies. We detected no differences between S4 and S4-Disc[1] mice
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