Table 1.
Summary of rotarod performance in mouse models with mutations in ASD risk genes.
| Human gene/CNV | Mouse model | Rotarod phenotype (reference) |
|---|---|---|
| 15q11-13 | patDp/+ (6.3 Mb duplication on chromosome 7) | Similar coordination, enhanced learning (Nakatani et al., 2009) |
| 16p11.2 | Delm (Mills model) | Similar coordination, enhanced learning (Lynch 3rd et al., 2020; Ouellette et al., 2020) Similar coordination, deficit in learning (Yin et al., 2021) |
| Dup/+ (Sult1a1-Spn interval) | Similar coordination, deficit in learning (Arbogast et al., 2016) | |
| 17p11.2 | Dp(11)17/+ | Similar coordination, deficit in learning (Ricard et al., 2010) |
| Df(11)17/+ | Deficit in coordination, similar learning (Ricard et al., 2010) | |
| ARHGAP32 (PX-RICS) | PX-RICS−/− | Deficit in coordination, deficit in learning (Nakamura et al., 2016) |
| ARID1B | Arid1b hKO | Deficit in coordination, deficit in learning (Shibutani et al., 2017) |
| Arid1b+/− | Similar coordination, deficit in learning (Jung et al., 2017) | |
| ARX | Arx(GCG)10 + 7 | Enhanced overall performance (Price et al., 2009) |
| Arxdup24/0 | Increased average latency to fall across 3 trials (Dubos et al., 2018) | |
| ATP1A3 | Atp1a3+/− | Enhanced overall performance (Ikeda et al., 2013) |
| CACNA1G | Cacna1g-Arg1723His-KI+/−, Cacna1g-Arg1723His-KI−/− | Deficit in coordination, deficit in learning (Hashiguchi et al., 2019) |
| CADM1 | Cadm1-KO | Deficit in coordination, deficit in learning (Takayanagi et al., 2010) |
| CDKL5 | Cdkl5−/y | Similar coordination, deficit in learning (Wang et al., 2012; Gao et al., 2020; Adhikari et al., 2022) Deficit in coordination, deficit in learning (Jhang et al., 2017) |
| Cdkl5+/−, Cdkl5−/− | Similar coordination, deficit in learning (Fuchs et al., 2018) | |
| CHD8 | Chd8+/E31T | Enhanced overall performance (Hulbert et al., 2020) |
| Chd8+/− | Similar coordination, enhanced learning (Platt et al., 2017) | |
| CNTNAP2 | Cntnap2−/− | Increased performance on a single trial (Penagarikano et al., 2011) Increased latency to fall from constant speed rotarod (Dawes et al., 2018) |
| CTNNB1 | Bfc/+ | Deficit in coordination, deficit in learning (Tucci et al., 2014) |
| CYFIP1 | Cyfip1+/tm2a(EUCOMM)Wtsi | Similar coordination, deficit in learning (Bachmann et al., 2019) |
| Cyfip+/− | Deficit in coordination, similar learning (Domínguez-Iturza et al., 2019) | |
| DDX3X | Ddx3x+/− | Similar coordination, deficit in learning (Boitnott et al., 2021) |
| DLG4 | Dlg4−/− | Deficit in coordination, deficit in learning (Feyder et al., 2010) |
| DSCAM | Dscamdel17/del17 | Deficit in coordination, deficit in learning (Xu et al., 2011) |
| DYRK1A | mBACtgDyrk1a (186n3) | Similar coordination, deficit in learning (Souchet et al., 2014) |
| EN2 | En2−/− | Similar coordination, deficit in learning (Brielmaier et al., 2012) Deficit in coordination, deficit in learning (Cheh et al., 2006) |
| FOXP2 | Foxp2 R552H/+ | Similar coordination, deficit in learning (Groszer et al., 2008) Deficit in coordination, deficit in learning (French et al., 2012) |
| Foxp2wt/ko | Similar coordination, deficit in learning (Enard et al., 2009) | |
| FMR1 | Fmr1−/− | Similar coordination, enhanced learning (Nolan et al., 2017) Enhanced overall performance (Roy et al., 2011) Similar coordination, deficit in learning (Bhattacharya et al., 2012; Uutela et al., 2012; Li et al., 2023) |
| Fmr1 CGG KI | Similar coordination, deficit in learning (Van Dam et al., 2005) | |
| GABRB3 | Gabrb3−/− | Similar coordination, deficit in learning (DeLorey et al., 1998) |
| p+/m- | Similar coordination, deficit in learning (DeLorey et al., 2011) | |
| p−/m+ | Similar coordination, deficit in learning (DeLorey et al., 2011) | |
| IL1RAPL1 | Il1rapl1 −/Y | Enhanced overall performance (Yasumura et al., 2014) |
| KDM5C | Kdm5c−/y | Decreased performance on a single trial (Scandaglia et al., 2017) |
| KIRREL3 | Kirrel3−/− | Similar coordination, enhanced learning (Hisaoka et al., 2018) |
| LRRC4 | Lrrc4−/− | Similar coordination, deficit in learning (Um et al., 2018) |
| MECP2 | Mecp2-308 | Similar coordination, deficit in learning (De Filippis et al., 2010) |
| Mecp2tm1Tam | Deficit in coordination, deficit in learning (Pelka et al., 2006) | |
| Mecp2tm1.1Jae | Deficit in coordination, deficit in learning (Morello et al., 2018) | |
| Tau-Mecp2 (overexpression) | Similar coordination, deficit in learning (Na et al., 2012) | |
| Mecp2tm1.Bird | Similar coordination, deficit in learning (Pratte et al., 2011) Deficit in coordination, deficit in learning (Kao et al., 2015; Vogel Ciernia et al., 2017) Decreased performance on a single trial (Santos et al., 2007) |
|
| Mecp2T158A | Deficit in coordination, deficit in learning (Goffin et al., 2011) | |
| Mecp2R168X | Decreased average latency to fall across 3 trials (Schaevitz et al., 2013) | |
| Mecp2R294X | Deficit in coordination, deficit in learning (Collins et al., 2022) | |
| Mecp2R306C | Decreased average latency to fall across 3 trials (Lyst et al., 2013) Decreased average latency to fall across 2–4 trials (Ebert et al., 2013) |
|
| Mecp2ΔAT-hook1 | Decreased average latency to fall across 3 trials (Xu et al., 2018) | |
| Mecp2TG (overexpression) | Similar coordination, enhanced learning (Collins et al., 2004, 2022; Sztainberg et al., 2015; Ash et al., 2021a,b) | |
| MYT1L | Myt1l+/− | Similar coordination, deficit in learning (Wohr et al., 2022) |
| NRXN1 | Nrxn1α KO | Similar coordination, enhanced learning (Etherton et al., 2009) |
| Nrxn1α+/ΔExon1, Nrxn1αΔExon1/ΔExon1 | Similar coordination, enhanced learning (Xu et al., 2023) | |
| Nrxn1α+/ΔExon9, Nrxn1αΔExon9/ΔExon9 | Similar coordination, enhanced learning (Xu et al., 2023) | |
| NLGN2 | Nlgn2−/− | Deficit in coordination, similar learning (Blundell et al., 2009) |
| Nlgn2+/− | Similar coordination, enhanced learning (Wohr et al., 2013) | |
| NLGN3 | Nlgn3−/− | Similar coordination, enhanced learning (Rothwell et al., 2014) |
| Nlgn3 R451C KI | Similar coordination, enhanced learning (Chadman et al., 2008; Rothwell et al., 2014; Cao et al., 2022) | |
| Nlgn3mf | Similar coordination, enhanced learning (Yoshida et al., 2021) | |
| NF1 | Nf1+/− | Similar coordination, deficit in learning (van der Vaart et al., 2011) |
| Nf123a−/− | Similar coordination, deficit in learning (Costa et al., 2001) | |
| NRP2 | Nrp2−/− | Similar coordination, deficit in learning (Shiflett et al., 2015) |
| NTNG1 | Ntng2−/− | Enhanced overall performance (Zhang et al., 2016) |
| OTUD7A | Otud7a−/− | Similar coordination, deficit in learning (Yin et al., 2018) |
| PAX5 | Pax5R31Q/− | Deficit in coordination, deficit in learning (Kaiser et al., 2022) |
| PTCHD1 | Ptchd1−/y | Decreased average latency to fall across 3 trials (Ung et al., 2018) |
| PTEN | Ptenm3m4/m3m4 | Deficit in coordination, deficit in learning (Tilot et al., 2014) |
| RAB39B | Rab39b−/− | Decreased average latency to fall across 3 trials (Wang et al., 2023) Similar coordination, deficit in learning (Niu et al., 2020; Zhang et al., 2020) |
| RELN | Reln ΔC-KI | Enhanced overall performance (Sakai et al., 2016) |
| Reln+/rl-Orl | Similar coordination, deficit in learning (Sobue et al., 2018) Deficit in coordination, deficit in learning (Lalonde et al., 2004) |
|
| SCN1A | Scn1a+/− | Similar coordination, deficit in learning (Beretta et al., 2022) |
| Scn1a+/R1407X | Enhanced coordination, similar learning (Ito et al., 2013) | |
| Scn1a+/A1783V | Similar coordination, enhanced learning (Miljanovic et al., 2021) Decreased average latency to fall across 3 trials (Ricobaraza et al., 2019; Fadila et al., 2020) |
|
| SCN2A | Scn2a+/− | Similar coordination, enhanced learning (Lena and Mantegazza, 2019) Deficit in coordination, deficit in learning (Tatsukawa et al., 2019) |
| Scn2a+/K1422E | Similar coordination, enhanced learning (Echevarria-Cooper et al., 2022) | |
| SHANK1 | Shank1−/− | Similar coordination, deficit in learning (Hung et al., 2008; Silverman et al., 2011) |
| SHANK3 | Shank3+/E13 | Similar coordination, enhanced learning (Jaramillo et al., 2017) |
| Shank3+/Δ4-22 | Similar coordination, deficit in learning (Drapeau et al., 2018) | |
| Shank3e4-9/e4-9 | Deficit in coordination, deficit in learning (Wang et al., 2011) | |
| Shank3E13/E13 | Similar coordination, deficit in learning (Jaramillo et al., 2017) | |
| Shank3Δ13-16/Δ13-16 | Similar coordination, deficit in learning (Peixoto et al., 2019) | |
| Shank3fx/fx | Deficit in coordination, deficit in learning (Mei et al., 2016) | |
| Shank3 InsG3680/ InsG3680 | Deficit in coordination, deficit in learning (Speed et al., 2015; Zhou et al., 2016) | |
| Shank3Δ11/Δ11 | Similar coordination, deficit in learning (Vicidomini et al., 2017) | |
| Shank3ΔC/ΔC | Deficit in coordination, deficit in learning (Kouser et al., 2013) | |
| Shank3−/− | Deficit in coordination, deficit in learning (Yang et al., 2012) | |
| SLC6A3 | DATT356M/T356M | Similar coordination, enhanced learning (DiCarlo et al., 2019) |
| SYNGAP1 | Syngap1+/− | Deficit in coordination, deficit in learning (Nakajima et al., 2019) Deficit in coordination, similar learning (Muhia et al., 2010) |
| TOP3B | Top3β−/− | Deficit in coordination, deficit in learning (Rahman et al., 2021) |
| TSC2 | Tsc2+/− | Similar coordination, enhanced learning (Benthall et al., 2021) |
| Tsc2ΔRG | Similar coordination, deficit in learning (Chevere-Torres et al., 2012) | |
| UBE3A | Ube3am−/p+ | Deficit in coordination, deficit in learning (Heck et al., 2008; Leach and Crawley, 2018; Sonzogni et al., 2018; Jiang et al., 1998; Miura et al., 2002; Mulherkar and Jana, 2010; Born et al., 2017; Huang et al., 2013) |
| Ube3am−/p- | Deficit in coordination, deficit in learning (Heck et al., 2008) | |
| Ube3aGenedel | Deficit in coordination, deficit in learning (Syding et al., 2022) | |
| Ube3aOE (overexpression) | Enhanced overall performance (Punt et al., 2022) | |
| Ube3amatT503A (gain of function) | Similar coordination, enhanced learning (Xing et al., 2023) | |
| WDFY3 | Wdfy3+/lacZ | Deficit in coordination, deficit in learning (Le Duc et al., 2019) |
ASD risk genes/CNVs depicted and references for a given model are representative and not exhaustive. Mouse models were chosen using the Simons Foundation Autism Research Initiative (SFARI) Gene mouse models module. Mouse models of ASD risk genes designated as Category 1 (high confidence gene) or Category 2 (strong candidate gene) by SFARI’s gene scoring system were considered. More information about SFARI gene and their gene scoring system can be found at gene.sfari.org. Mouse studies that failed to detect a phenotype are not presented, nor are models that utilized cell-type specific perturbation.