Table 2.

Genetic models of autism

Gene/ Protein/ Function	Animal models	Behavioral alterations	Cerebellar pathology	Strengths	Caveats	Refs
RORα	Staggerer mice	Ataxia Impaired reversal learning Perseverative behavior Abnormal responses to novelty	Loss of PC A disappearance of granule cells Severe hypoplasia	Face validity	Limited relation to human cases Widespread effects	Herrup and Mullen, 1979; Herrup et al., 1996; Doulazmi et al., 2001; Goldowitz and Koch, 1986; Misslin et al., 1986; Lalonde et al., 1996
SHANK3 Postsynaptic protein IB2	KO mice	Social abnormalities Stereotypy Poor learning and memory	Altered glutamatergic transmission Abnormal dendritic arborization of PC	Gene implicated in humans Face validity	No cell type-regional- or time-dependent manipulation	Beri et al., 2007; Peça et al., 2011; Jiang and Ehlers, 2013
ENGRAILED 2 a transcription factor	KO mice	Attenuated play Reduced aggressive and non-aggressive social behaviors Impaired learning	Hypoplasia Decreased number of PC Foliation abnormalities	Gene implicated in humans Face validity	No cell type-regional- or time-dependent manipulation	Millen et al., 1994; Kuemerle et al., 1997, 2007; Cheh et al., 2006; Brielmaier et al., 2012
FMR1 the fragile X mental retardation protein	KO mice	Hyperactivity Perseverative behavior Poor learning and memory	Elongated spines on PC Reduced volume of the cerebellar nuclei	Gene implicated in humans Face validity	No cell type-regional- or time-dependent manipulation	Koekkoek et al., 2005; Olmos-Serrano et al., 2011; Ellegood et al., 2010; Yuskaitis et al., 2010
TSC1 and 2 hamartin (TSC1) and tuberin (TSC2)	Conditional PC KO mice	TSC1 KO mice Abnormal social interaction Repetitive behavior and altered ultrasonic vocalizations TSC2 KO mice Repetitive behavior Decreased sociability	A progressive PC loss	Gene implicated in humans PC- and time-specific Amenable to treatment Face validity	Later effects of PC loss confound the phenotypes	Reith et al., 2011, 2013; Tsai et al., 2012
FOXP2 Transcriptional factor	Foxp 2 KO mice Foxp2 (R552H) knock-in	Motor impairment Altered ultrasonic vocalization	Thick EGL at P15-17 Thinning of the molecular layer Ectopic PC Underdeveloped dendrites Misaligned Bergman glia	Gene and mutation implicated in humans Face validity	No cell type-regional- or time-dependent manipulation	Shu et al., 2005; Fujita et al., 2012a-c
GABA receptors	Gabrb3 KO mice	Deficient sociability and nesting behavior	Hypoplasia of the vermis	Face validity	Limited relation to human cases Widespread effects	DeLorey et al., 2008