We first tested whether
Shank3ΔC ASD model mice exhibited sleep disruption during development. We measured total sleep amount and bout lengths in male and female
Shank3WT/ΔC heterozygotes,
Shank3ΔC/ΔC homozygotes, and wild-type (WT) littermates, at two developmental time points: juvenile (P25–P41) and adolescent (P42–P56). Our goals were to determine if developing
Shank3ΔC exhibits sleep disruption, and to determine when this phenotype emerges. Wake and sleep behavior was monitored for an average of 8–10 uninterrupted days using PiezoSleep, a noninvasive piezoelectric home-cage recording system previously validated using simultaneous EEG/EMG and video recordings [
29‐
31]. Average daily total sleep amount and bout lengths were calculated from repeated days of uninterrupted recording for each individual to yield a robust measurement of typical daily sleep behavior. PiezoSleep requires that mice be single housed during recording. Therefore, separate cohorts were generated for the juvenile and adolescent groups in order to mitigate the lasting negative effects of social isolation during development [
35]. In juveniles and adolescents of both sexes we observed that
Shank3ΔC/ΔC mice show a significant reduction in total daily sleep compared to WT littermates (1-way ANOVA followed by Tukey’s multiple comparisons test, WT:
Shank3ΔC/ΔC, juvenile males
p < 0.0001; juvenile females
p = 0.0004; adolescent males p = 0.0021; adolescent females
p = 0.009). Reduced sleep amount in juveniles was significant in the light and dark phases (Fig.
1A-D). Additionally, in adolescent
Shank3ΔC/ΔC mice compared to WT, we observed reductions in sleep bout length in the light phase in the female group (female
p = 0.0053; male closely approached significance at
p = 0.0532) and both sexes in the dark phase (male
p = 0.0199, female
p = 0.0215) (Fig.
1C, D). Post hoc tests did not reveal any significant differences in sleep amount or bout length between WT littermates and
Shank3WT/ΔC heterozygotes in either sex or age (Fig.
1A-D, complete reporting of statistical analysis is shown in Additional file
1). Overall, the data show that male and female
Shank3ΔC/ΔC mice have reduced total sleep detected in juveniles as an early phenotype, and that sleep additionally becomes fragmented as the animals enter adolescence. These findings are in agreement with a recent study describing reduced sleep in developing homozygous Shank3 InsG3680 ASD model mice [
10]. Additionally, the worsening (fragmentation) of sleep behavior during adolescence in
Shank3ΔC/ΔC homozygous mice matches observations obtained from some Phelan–McDermid syndrome patients during the transition to adolescence [
21,
27,
36]. Together with a previous report describing sleep disruption in male adult
Shank3ΔC/ΔC mice [
27], our findings show that sleep disruption in
Shank3ΔC/ΔC mice has an early onset that persists throughout the lifespan.