General and social anxiety in the BTBR T+ tf/J mouse strain

Abstract

BTBR T+ tf/J (BTBR) is an inbred mouse strain that shows behavioral traits with analogies to the three diagnostic symptoms of autism spectrum disorder (ASD); deficits in social interaction, impaired communication, and repetitive behaviors with restricted interests. Previous findings reveal that when compared to C57BL/6J (B6) and other inbred strains, BTBR exhibit normal to low anxiety-like traits in paradigms designed to assess anxiety-related behaviors. The current study assessed the generality of these anxiety findings. In experiment 1, B6 and BTBR mice were tested in the elevated plus maze (EPM), mouse defense test battery (MDTB) and elevated zero-maze. BTBR mice exhibited an anxiogenic profile in the EPM, with a reduction in open arm time and an increase in risk assessment behaviors, as compared to B6. In the MDTB, BTBR showed enhanced vocalization to the predator, and significantly less locomotor activity than B6 in the pre-threat situation, but significantly more locomotion than B6 following exposure to a predator threat, suggesting enhanced defensiveness to the predator. In the zero-maze, BTBR mice showed a significantly higher number of entries and time spent in the open segments of the apparatus, when compared to B6. In experiment 2, a three-chambered social preference test was used to evaluate effects of the systemic administration of an anxiolytic compound, diazepam, on B6 and BTBR social approach. Diazepam consistently increased time in the compartment containing the social stimulus, for both B6 and BTBR mice. However, in the vehicle treated groups, B6 mice spent significantly more time while BTBR mice spent significantly less time in the social stimulus compartment; after diazepam administration both B6 and BTBR strains significantly preferred the social stimulus chamber. These results suggest that while the anxiety responses of BTBR mice to novel situations (EPM and zero-maze) are inconsistent, BTBR mice appear to be more defensive to animate threat stimuli (predator or another mouse). Reduction of anxiety by diazepam normalized the social preference of BTBR for a mouse stimulus in the three-chambered test.

Automated long-term tracking and social behavioural phenotyping of animal colonies within a semi-natural environment

“…4e). These findings strongly support previous studies that suggested a social behaviour deficiency in the BTBR mouse strain 29,31 . Moreover, we found that by using four social behaviour features collected by the system in a single testing day, we could predict the mouse strain with an accuracy of about 90-95% (see Methods and Supplementary Fig.…”

“…The integrated video-RFID system was applied to test two inbred mouse strains: C57BL/6 Â 129Sv (C57 Â 129) and BTBR T þ tf/J (BTBR), which were previously reported to exhibit significantly different behavioural phenotypes [29][30][31] . Three independent groups of mice were tested for each of the mouse strains (that is, a total of six experiments), using an identical standard operation protocol; the duration of each experiment was 8 days.…”

Aberrant IgG isotype generation in mice with abnormal behaviors

“…Further, these types of mice have been analyzed using various behavioral tests including an elevated plus maze, a mouse defense battery, an elevated zero-maze, a three-chambered social approach test, etc. (Bolivar et al, 2007;Meyza et al, 2013;Moy et al, 2007;Pobbe et al, 2011;Silverman et al, 2010;Wohr et al, 2011). Since numerous immune abnormalities have been reported in autism (Ashwood & van de Water, 2004;Stigler et al, 2009), the current study investigated the immune system of BTBR mice.…”

Inchworming: A Novel Motor Stereotypy in the BTBR <em>T⁺ Itpr3^tf</em>/J Mouse Model of Autism

“…Under these conditions, the BTBR mice still inchworm, but at a lower frequency and duration, thus indicating that the inchworming behavior is a stereotypic behavior possibly induced by social anxiety (data not shown). However, given that studies have failed to reliably demonstrate differences in anxiety between the BTBR and B6 control mice, anxiety is likely a interacting with other factors to induce this behavior 12 . However, the focus of this methodological article was the standardized modification to the juvenile social interaction protocol because it elicits the behavior rapidly and reliably, with dramatic differences between BTBR and B6 mice.…”