Low home cage social behaviors in BTBR T+tf/J mice during juvenile development

Abstract

BTBR T+tf/J (BTBR) is a genetically homogenous inbred strain of mice that displays abnormal social behaviors, deficits in vocalizations, and high levels of repetitive behaviors, relevant to the three diagnostic symptoms of autism spectrum disorder, leading to the use of this strain as a mouse model of autism. Comprehensive observations of BTBR social behaviors within the home cage during early stages of development have not been conducted. Here we evaluate the home cage behaviors of BTBR in two laboratory environments (NIMH, Bethesda, Maryland vs. UC Davis, Davis, California), starting from the day of weaning and continuing into adulthood. Extensive ethogram parameters were scored for BTBR in home cages that contained four BTBR conspecifics, versus home cages that contained four C57BL/6J (B6) conspecifics. BTBR were considerably less interactive than B6 in the home cage at both sites, as measured during the early dark stage of their circadian cycle. A novel home cage behavioral measure, frequency of long interactions, was found to be more frequent and of longer duration in B6 versus BTBR home cages across experimental sites. Significant strain differences in the occurrence of investigative and affiliative behaviors were also seen, however these findings were not fully consistent across the two testing sites. At the end of the 30-day home cage observation period, each seven-week old subject mouse was tested in the three-chambered social approach task. BTBR displayed lack of sociability and B6 displayed significant sociability, consistent with previous reports. Our findings reveal that BTBR engaged in lower levels of some components of spontaneous conspecific social interactions in the home cage environment throughout juvenile development, consistent with their deficits in juvenile and adult sociability as measured in specialized social tasks.