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Fig. 6 | Molecular Autism

Fig. 6

From: Neuroanatomy and behavior in mice with a haploinsufficiency of AT-rich interactive domain 1B (ARID1B) throughout development

Fig. 6

Arid1b+/− exhibited mild ASD-relevant social communication phenotypes in the direct reciprocal social interaction and seizure susceptibility but no repetitive behavior. Three-chambered social approach is a standard measure of social behavior. It was used as a preliminary evaluation tool for sociability. While both genotypes exhibited normal social approach, i.e., they spent more time in the chamber with a novel mouse or time sniffing the novel mouse compared to a novel object), the Arid1b+/− made fewer total entries during the task. a Arid1b+/− showed no deficits compared to Arid1b+/+ littermates in 3-chambered social approach in time spent in chamber with the novel mouse, b time spent sniffing the novel mouse compared to novel object also indicated sociability in both genotypes. c Arid1b+/− made fewer transitions compared to Arid1b+/+. df Next, we moved to a more sensitive task to observe social dyad interactions. During male–female social dyad interactions, males are introduced to a Arid1b+/+, novel estrous female for 5 min in a novel, clean environment and social investigative and situational behaviors are evaluated and male-emitted ultrasonic vocalizations (USVs) are counted. d Adult Arid1b+/− males spent less time nose-to-anogenital sniffing and e less time in a following posture/behavior, the two main components of this interaction, indicating reduced social behavior in this task. f Arid1b+/− males also emitted fewer USVs during the dyad interactions compared to Arid1b+/+ male littermates which also suggested impaired social communication. g No increased or decreased self-grooming was observed. hi We used a gold standard assay of anxiety, the elevated plus maze, to observe anxiety-like behavior. h Arid1b+/− spent fewer total seconds on the open arm which usually indicates anxiety-like behavior. i Arid1b+/− also showed fewer total entries between arms, which suggests this task may be confounded by the data in Fig. 2, the robust motoric deficit. jl With a high concordance of epilepsy in ASD, and excitatory inhibitory balance being a prominent theory, we investigated seizure susceptibility in Arid1b+/−. Mice are injected intraperitoneally with pentylenetetrazol (PTZ) chemoconvulsant, and latency to seizure events including loss of righting, tonic–clonic seizure and death were recorded. j Arid1b+/− showed seizure vulnerability and susceptibility by decreased in time to loss of righting after PTZ administration (k) faster onset to tonic–clonic extension and l latency to death, compared to Arid1b+/+. For ac, Arid1b+/+ N = 28, Arid1b+/− N = 25, for df Arid1b+/+ N = 15, Arid1b+/− N = 17, in g, Arid1b+/+ N = 28, Arid1b+/− N = 25, for g and h, Arid1b+/+ N = 28, Arid1b+/− N = 27, for jl, Arid1b+/+ N = 45, Arid1b+/− N = 40. * p < .05 versus Arid1b+/+ by repeated-measures two-way ANOVA or Student’s unpaired t test. Error bars represent mean ± SEM

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