Expression of social behaviors of C57BL/6J versus BTBR inbred mouse strains in the visible burrow system

Abstract

The core symptoms of autism spectrum disorder (ASD) include deficits in social interaction, impaired communication, and repetitive behaviors with restricted interests. Mouse models with behavioral phenotypes relevant to these core symptoms offer an experimental approach to advance the investigation of genes associated with ASD. Previous findings demonstrate that BTBR T+ tf/J (BTBR) is an inbred mouse strain that shows robust behavioral phenotypes with analogies to all three of the diagnostic symptoms of ASD. In the present study, we investigated the expression of social behaviors in a semi-natural visible burrow system (VBS), during colony formation and maintenance in groups comprising three adult male mice of the same strain, either C57BL/6J (B6) or BTBR. For comparative purposes, an extensively investigated three-chambered test was subsequently used to assess social approach in both strains. The effects of strain on these two situations were consistent and highly significant. In the VBS, BTBR mice showed reductions in all interactive behaviors: approach (front and back), flight, chase/follow, allo-grooming and huddling, along with increases in self-grooming and alone, as compared to B6. These results were corroborated in the three-chambered test: in contrast to B6, male BTBR mice failed to spend more time in the side of the test box containing the unfamiliar CD-1 mouse. Overall, the present data indicates that the strain profile for BTBR mice, including consistent social deficits and high levels of repetitive self-grooming, models multiple components of the ASD phenotype.

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

“…Normal 3-chambered social approach appeared in mice with mutations in genes including oxytocin [24], Shank1 [25], Nlgn2 [26], Ephrin-A [27] and 16p11.2 deletion [28] Variable findings on social approach across laboratories and in mouse lines generated on different genetic backgrounds have been reported for mutations including Fmr1 [29,30], Nlgn3 [31][32][33][34], and Nlgn4 [35,36]. Social deficits on the 3-chambered sociability have been wellreplicated in 2 inbred strains of mice, BTBR [10,12,[37][38][39][40][41][42][43][44] and Balb/cJ [45,46].…”

“…The most well described and examined is the BTBR T+ Itpr3tf/J (BTBR) inbred strain, in which deficits in a variety of social tasks, along with high repetitive self-grooming, marble burying, and digging, have been replicated by many laboratories [10,37,38,40]. In addition, the BALB/cJ (BALB) inbred strain displays strong social deficits at juvenile ages [45,147,148], and the C58/J inbred strain displays repetitive jumping [52].…”

Social propinquity in rodents as measured by tube cooccupancy differs between inbred and outbred genotypes

“…The assay has been used to establish various inbred (e.g., BTBR T+tf/J) and mutant (e.g., Fmr1-null) mouse strains as "autistic-like" mouse models (2). As an alternative to the three-chamber test, one may record the appearance of myriad social behaviors (e.g., anogenital and noseto-nose sniffing, chasing, wrestling, allogrooming) in the home cage, a visible burrow, or a neutral environment (3,4). Such comprehensive recording is extremely labor intensive and prone to errors (5) and is almost impossible to automate using present technology, although some progress is being made using machinelearning algorithms (6).…”

Autoimmune Disorder and Autism

“…Anatomically BTBR mice get total absence of the corpus callosum, and severely reduced hippocampal commissure, which are also attributed to their phenotypes [259][260][261][262]. Although primarily used as type 2 diabetes model [263][264][265][266][267][268] and phenylketonuria (PKU) model [269][270][271][272][273][274], BTBR mice were recently found to be a promising mice model for autism research because they exhibited the three core symptoms for diagnosing autism [275][276][277][278][279][280][281][282]. Using this strain, several groups have begun to explore the pathogenesis of autism.…”