Table 3.
Summary of published studies using activity monitoring in 12:12 hours light:dark cycle and in the absence of light to measure sleep and circadian rhythms in rodent models of ASD. Only genes and copy number variants (CNVs) reported in the Simons Foundation Autism Research Initiative gene database (SFARI GENE) are reported. Out of the 304 mouse/rat CNV/gene models reported, 17 have been used to study circadian rhythms. SFARI evidence scores categorize genes based on evidence supporting a gene’s relevance to ASD risk. Categories defined by SFARI database are as follows: 1 (High Confidence), 2 (Strong Candidate), 3 (Suggestive Evidence), 4 (Minimal Evidence), 5 (Hypothesized), S (Syndromic) (Zheng et al., 2001; Dudley et al., 2003; Meredith et al., 2006; Kozlov et al., 2007; Zhang et al., 2008; Sahar et al., 2011; Han et al., 2012; Wither et al., 2012; Lacaria et al., 2013, 2013, 2013 p.1; Ehlen et al., 2015; Kalume et al., 2015; Li et al., 2015; Tsuchiya et al., 2015; Jaaro-Peled et al., 2016; Diessler et al., 2017; Lipton et al., 2017; Saré et al., 2017; Ingiosi et al., 2019).
| CNV/Gene | PMID | SFARI Evidence | Activity monitoring in 12:12 h light:dark cycle | Activity monitoring in the absence of light |
|---|---|---|---|---|
| 17p11.2 (Mouse) | 23703963 | N/A | Reduced total running wheel activity | Reduced free running period length. Reduced total running wheel activity |
| Shank3 (Mouse) | 30973326 | 1, S | Reduced amplitude of running wheel activity | Reduced amplitude of running wheel activity with normal period length |
| Fmr1 (Mouse) | 28919851 | S | Shorter sleep duration in light period under homecage activity monitoring | Not recorded |
| Fmr1 (Mouse) | 18589395 | S | Fmr1 and Fxr2 knock out mice show no difference in wheel running compared to wild types. Fmr1/Fxr2 double knock out mice show loss of rhythmic activity | Fmr1 and Fxr2 knock out mice show shorter-free running period in constant dark and loss of rhythmic activity. Fmr1/Fxr2 double knock our mice show loss rhythmic activity |
| Tsc1andTsc2 (Mouse) | 28746872 | 1 | No difference in wheel running activity | Shorter free running period with no change in circadian amplitude or overall activity |
| Ube3a (Mouse) | 26446213 | 1 | No difference in circadian period or overall activity | No difference in circadian period or overall activity |
| Mecp2 (Mouse) | 26456390 | 1 | No difference in circadian rhythm | No difference in period length. Decrease in wheel running activity |
| Mecp2 (Mouse) | 25779967 | 1 | Reduced total wheel running activity, reduced alpha length and increased fragmentation of wheel running | Reduced total wheel running activity. Increase in-free running period length, decreased alpha length and increased fragmentation of wheel running |
| Mecp2 (Mouse) | 22523589 | 1 | Decrease in activity bout length but no difference in number of bouts (home cage activity monitoring) | Not reported |
| Rai1 (Mouse) | 28548639 | 1 | Decreased overall running wheel activity, decreased running wheel activity in the light period | Increase phase advance and increase in alpha length |
| Rai1 (Mouse) | 23703963 | 1 | Decrease total running wheel activity | Decreased period length and decreased total running wheel activity |
| Scn1a (Mouse) | 22223655 | 1 | Delayed phase of activity onset. Reduced total wheel running activity | Increased period length. Reduced total wheel running activity |
| Scn1a (Mouse) | 25766678 | 1 | Reduced total wheel running activity | Reduced total wheel running activity |
| Disc1 (Mouse) | 27354230 | 2 | Decreased activity during the dark period | No difference in circadian period |
| Magel2 (Mouse) | 17893678 | 2, S | No difference in wheel running activity | Reduced amplitude of running wheel activity with reduced activity in the subjective dark period |
| Cd38 (Mouse) | 21937766 | 3 | Reduced total locomotor activity | Shorter period length |
| Kcnma1 (Mouse) | 16845385 | 3 | Decreased amplitude of locomotor activity | Increase in period length. Decreased amplitude of locomotor activity |
| Npas2 (Mouse) | 12843397 | 4 | Increased running wheel activity during the dark period | Shorter period length |
| Per1 & Per2 (Mouse) | 11389837 | 4 | No difference in wheel running activity | PER1 mutants have a shorter period length. PER1 mutants and PER1/PER2 double mutants have no circadian rhythm |
| Rasd1 (Mouse) | 23703963 | 5 | No difference in wheel running | Female mice displayed reduced free running period lengths |