Table 1.

Description of behavioral and biological phenotypes for five mouse models of autism

Mouse model	Phenotypes	References
Fragile X	Fragile X syndrome is the most common genetic cause of mental retardation. Fmr1 mutant mice deficient in the FMRP protein displayed endophenotypes relevant to components of Fragile X. Phenotypes included elevated locomotor activity in an open field, anxiety-like behaviors in the mirrored chamber test, audiogenic seizures, macroochidism, and low prepulse inhibition of acoustic startle. Attentional deficits and impairment in inhibitory control (impulsivity) were detected in the five choice serial reaction time task. Fmr1 mutant mice engaged in more sniffing of a familiar partner in the partition test, and won fewer social dominance challenges. Impairments in spatial learning of the Morris water maze were accompanied by resistance to change during the reversal phase. Increased spine density and length were reported for the somatosensory cortex, while reduced dendritic spine density and length were reported for the hippocampus. Long-term potentiation was found to be impaired, and long-term depression enhanced, in Fmr1 mutant mice.	Bakker (1994), Beckel-Mitchener and Greenough (2004), Bilousova et al. (2009), D’Hooge et al. (1997), Dolen et al. (2007), Errijgers et al. (2008), Lauterborn et al. (2007), Moon et al. (2006), Paylor et al. (2008), Peier et al. (2000), Spencer et al. (2005)
Chr 15q11–13	Deletions and duplications in the 15q11–13 chromosomal region are associated with Angelman’s syndrome, Prader–Willi syndrome, and autism. Mice with a paternally transmitted duplication on the homologous region of mouse chromosome 7 displayed impaired sociability in the three-chambered social approach task. Anxiety-like phenotypes were detected on the elevated plus-maze. More ultrasonic vocalizations were emitted by pups separated from their dams, while fewer vocalizations were emitted by adults in the resident-intruder test. PatDp/+ paternal duplication mice were normal on acquisition but failed on the reversal phase in both the Morris water and the Barnes maze, indicating an inability to reverse a spatial habit. Higher freezing in the altered context was reported for fear conditioning, indicating impaired learning and memory	Nakatani et al. (2009)
Pten	Mutations in phosphatase and tensin homolog deleted on chromosome ten (PTEN) are associated with cancers, seizures, macroencephaly, mental retardation, and autism. Mice with a conditional Pten mutation on a neuron-specific promoter exhibited seizures, macroencephaly, and dendritic hypertrophy. Increased acoustic startle and lower prepulse inhibition indicated hypersensitivity to sensory stimuli. Social interaction deficits were detected during juvenile reciprocal interactions, sociability in the three-chambered social approach task, preference for social novelty, and nest building. Impaired spatial learning with high thigmotaxis was found in Pten mutants in the Morris Water Maze test. Many of the neuroanatomical and behavioral abnormalities in Pten mutant mice were reversed by treatment with the mTOR inhibitor rapamycin.	Kwon et al. (2006), Zhou et al. (2009)
BTBR	BTBR T+ tfJ (BTBR) is a genetically homogenous, commercially available inbred strain of mice, included in the top tier of the Mouse Phenome Project (http://phenome.jax.org/). BTBR juveniles and adults display low levels of reciprocal social interactions, lack of sociability in the automated three-chambered social approach task, and reduced social transmission of food preference, as compared to social strains such as C57BL/6J and FVB/NJ. BTBR displays high levels of spontaneous self-grooming both as juvenile and as adults. More frequent and louder ultrasonic vocalizations were emitted by BTBR pups separated from their dams, while fewer vocalizations are emitted by adults in response to female urinary pheronome cues, as compared to C57BL/6J. Measures of general health, motor functions, and sensory abilities including olfaction are normal in BTBR, supporting an interpretation of highly selective abnormalities in traits relevant to the diagnostic symptoms of autism.	Bolivar et al. (2007), McFarlane et al. (2008), Moy et al. (2007), Scattoni et al. (2008a, b), Yang et al. (2007a, b, 2009), Wöhr et al. (2010)
Prenatal valproic acid	A small number of cases of autism were linked with valproic acid (VPA) medication taken by mothers during pregnancy. Rats from dams treated with VPA during pregnancy demonstrate reduced social interactions as juveniles, and low sociability as adults on the social approach task. VPA-treated rat pups display delays in olfactory discrimination during nest-seeking behavior. Repetitive/stereotyped patterns of behavior were observed in VPA rats placed in an open field. Lower sensitivity to painful stimuli as measured by tail flick and thermal paw withdrawal tests, but increased sensitivity to nonpainful stimuli as measured in tactile test (von Frey filaments) have been reported. VPA-treated rats display enhanced responses on eye blink conditioning, and impaired spatial learning in the Morris Water maze. Cerebellar pathology, increased complexity of apical dendritic arborization, and reduced excitatory synaptic responses have been observed in VPA-treated rats, as well as increased numbers of NMDA receptors and hyperconnectivity. Altered levels of monoamines, elevated brain serotonin, and disturbance of sleep patterns have been described. Mice treated prenatally with VPA have reduced expression of neuroligin-3, a cell adhesion protein involved in synapse formation, in hippocampus and somatosensory cortex.	Ingram et al. (2000), Kolozsi et al. (2009), Narita et al. (2002), Rinaldi et al. (2007), Rodier et al. (1996), Schneider and Przewlocki (2005), Snow et al. (2008), Stanton et al. (2007), Tsujino et al. (2007), Wagner et al. (2006)