Analysis of genes within the schizophrenia-linked 22q11.2 deletion identifies interaction of night owl/LZTR1 and NF1 in GABAergic sleep control
Fig 2
Neuronal loss of the LZTR1 homolog night owl (nowl) reduces night-time sleep in Drosophila.
(A) Daily sleep profiles across a 12-hour light, 12-hour dark (white and black bars) cycle for controls (elav>+ and nowl-RNAi/+) compared to elav>nowl-RNAi. Sleep data are binned into 30-minute intervals. (B) Schematic of the nowl locus. The gene comprises 5′ and 3′ untranslated regions (light grey) and a multi-exon coding region (dark grey). The locations of the 6-kb Mi{ET1} Minos transposable element inserted in the nowl1 allele and the guide-RNA (gRNA) target sites used to induce the nowlKO CRISPR/Cas9-mediated lesion are indicated. (C, D) Sleep profiles for (C) male nowl1/Y and (D) female nowl1/nowl1 mutant flies, compared to control genotypes [in C: w1118 nowl+/Y (w1118/Y) and w+ nowl+/Y (+/Y); in D: w1118/1118 and nowl1/+]. (E-F) Total day- and night-time sleep (minutes) in male and female flies. (E) Total daytime sleep in male and female nowl1 mutant flies. (F) Total nighttime sleep is significantly decreased in hemizygous male and homozygous female nowl1 mutants, but not in heterozygous females. (G) Overall total sleep (min.) in male and female nowl1 mutant flies compared to controls. Loss of nowl in male flies significantly decreases total sleep compared to controls. (H) Sleep latency measured for male and female nowl1 mutant flies compared to controls. Loss of nowl in both male and female flies significantly increases sleep latency compared to controls. (I) Quantification of motion-bout activity (min.) during night. Motion-bout activity during the night is significantly reduced in nowl-knockdown flies. Graphs represent means with SEM (n = 32–92) of data pooled from one to three independent experiments. Significance was determined using Kruskal-Wallis test with Dunn's post-hoc testing (* p<0.05, ** p<0.01, *** p<0.001).