Table 1.

Examples of autism-relevant behaviours in genetic mouse models of autism spectrum disorders

Mouse model	Genetic characteristics	Behavioural phenotypes relevant to the symptoms of autism*
Nlgn4	Null mutation in the murine orthologue of the human NLGN4 gene43	Reduced reciprocal social interactions43 Low sociability43 Lack of preference for social novelty43 Reduced ultrasonic vocalizations43
Nlgn3	Homozygous mutation of humanized R451C mutation of the Nlgn3 gene44,45	No genotype differences in reciprocal social interactions44,45 No genotype differences in sociability44,45 No genotype differences in preference for social novelty44 Reduced ultrasonic vocalizations44
	Null mutation in the murine orthologue of the human NLGN3 gene41	No genotype differences in reciprocal social interactions41 Reduced preference for social novelty41
Neurexin 1α	Null mutation in the murine neurexin 1α generated by deleting the first exon of the gene46	No genotype differences in reciprocal social interactions46 No genotype differences in sociability46 Impaired nest-building behaviour46 Increased repetitive self-grooming46
Nlgn1	Null mutation in the murine orthologue of the human NLGN1 gene47	No genotype differences in reciprocal social interactions47 No genotype differences in sociability47 No genotype differences in preference for social novelty47 Impaired nest-building behaviour47
Pten	Conditional null mutation, inactivated in neurons of the cortex and hippocampus, mouse orthologue of the human PTEN gene68	Reduced reciprocal social interactions68 Low sociability68 Impaired nest-building behaviour68 Impaired social recognition68
	Pten haploinsufficent mutant line in which exon 5, and thus the core catalytic phosphatase domain, is deleted48	Low sociability in females48
En2	Null mutation in the murine orthologue of the human EN2 gene49,50	Reduced reciprocal social interactions49 Increased repetitive self-grooming49 No genotype differences in sociability, confounded by low activity levels50
15q11–13	Duplication in the genomic region on the mouse chromosome 7 homologous to the human genomic region 15q11–13 (REF. 29)	Low sociability29 Ultrasonic vocalizations elevated in pups and reduced in adults29 Impaired reversal learning29
17p11.2	Duplication in the genomic region of murine chromosome 11 homologous to the human genomic region 17p11.2 (REF. 51)	Low sociability51 No genotype differences in preference for social novelty51 Impaired nest-building behaviour51
Gabrb3 ‡	Null mutation in the murine orthologue of the human GABRB3 gene52	Low sociability‡ (REF. 52) Lack of preference for social novelty‡ (REF. 52) Repetitive stereotyped circling patterns‡ (REF. 52) Impaired nest-building behaviour‡ (REF. 52)
Slc6a4	Null mutation in the murine orthologue of the human serotonin transporter (SLC6A4) gene50	Low sociability50 Lack of preference for social novelty50
	Haploinsufficient mutant line of the human serotonin transporter SLC6A gene48	Impaired social recognition48
Oxt	Null mutation in the murine Oxt gene generated by either a deletion in the first exon40,53,54 or by deletions in the last two exons40	Impaired social recognition53 Reduced pup ultrasonic vocalizations54 No genotype differences in sociability40 No genotype differences in preference for social novelty40
Avpr1b	Null mutation of the murine vasopressin receptor 1b Avpr1b gene55,56	Impaired social recognition55 Reduced pup ultrasonic vocalizations56
Mecp2	Heterozygous mutation in methyl-CpG-binding protein 2 (REFS 39,57,58,59)	Hindlimb clasping57,58 Social avoidance39 Impaired social recognition59 Reduced social interest in an arena59
Fmr1	Null mutant mouse with a targeted mutation in the Fmr1 gene in three genetic backgrounds: C57BL/6J38,50,60,61; hybrid of FVB/NJ × C57BL/6J62; and FVB/N-129/OlaHsd50	Increased social approach60,61 Reduced reciprocal social interactions38 No genotype differences in sociability62 No genotype differences in preference for social novelty62 Low sociability dependent on genetic background50 No genotype differences in preference for social novelty50
Tsc	Heterozygous mutation that replaces the second exon in the Tsc2 gene63	No genotype differences in sociability63
	Heterozygous mutation generated by replacing exons 6–8 in the Tsc1 gene65	Reduced reciprocal social interactions65 Impaired nest-building behaviour65
Foxp2	Homozygous and heterozygous mutations in the mouse homologue of the FOXP2 gene64 Knock-in mice for the mouse homologue of FOXP2 (REF. 67)	Reduced pup ultrasonic vocalizations64,67
Fgf17	Null mutation in the murine Fgf17 gene generated by deletion of the sites that encode the signal peptide66	Reduced reciprocal social interactions66 Lack of preference for social novelty66 Reduced pup ultrasonic vocalizations66
Cadps2	Null mutation in murine orthologue of the Cadps2 gene25	Reduced reciprocal social interactions25
BTBR	BTBR T + tf/J (BTBR strain) is a genetically homogenous inbred strain that displays behavioural traits with face validity to all three diagnostic symptoms of autism	Reduced reciprocal social interactions78,81,90,91,111 Low sociability81,83,88,90,91,111 Increased repetitive self-grooming81,88,90,111 Reduced social transmission of food preference81 Ultrasonic vocalizations elevated in pups and reduced in adults87,89 Unusual ultrasonic vocalization call categories in pups and adults87,135
BALB	BALB/cJ and BALB/cByJ are genetically homogenous inbred strains that display relatively low social behaviour in various settings, reduced ultrasonic vocalizations and reduced empathy-like behaviour	Low sociability79,83 No genotype differences in preference for social novelty83 Reduced reciprocal social interactions84 Reduced ultrasonic vocalizations in adolescent same-sex social interaction84 Reduced place-conditioned social reward85 Reduced social learning during social distress‡ (REFS 80,145)
C58/J	C58/J is a genetically homogenous inbred strain that displays low sociability, primarily in males, and high levels of two distinct repetitive behaviours that emerge early in development	High level of repetitive motor stereotypies82,86 Low sociability82,86 Increased repetitive self-grooming86

^*Behavioural tests are described in the main text.

^‡Phenotypes of survivors.

Avpr1b, arginine vasopressin receptor 1b; Cadps2, Ca²⁺-dependent activator protein for secretion 2; En2, engrailed 2; Fgf17, fibroblast growth factor 17; Fmr1, fragile × mental retardation syndrome 1; Foxp2, forkhead box protein 2; Gabrb3, gamma-aminobutyric acid A receptor, subunit beta 3; Mecp2, methyl-CpG-binding protein 2; Nlgn, neuroligin; Oxt, oxytocin; Pten, phosphatase and tensin homologue; Slc6a4, solute carrier 6 member 4; Tsc, tuberous sclerosis.