Inbred strain preference in the BTBR T+ Itpr3tf/J mouse model of autism spectrum disorder: Does the stranger mouse matter in social approach?

: BTBR T+ Itpr3tf /J (BTBR) mice have been used as a model of autism spectrum disorder (ASD) due to their low levels of sociability and high levels of repetitive grooming. These experiments explored social behavior in the BTBR and C57BL/6J mice using variations of the three-chambered social approach test. In the first test, the subject mice had a choice between a stranger mouse of the same strain or from a strain with a different level of sociability. The BTBR male mice demonstrated a strong preference for the more social C57BL/6J stranger mouse, as did the C57BL/6J male mice, although more moderately with sniff time only. The C57BL/6J female mice showed a moderate preference, sniff time only, for the BTBR stranger mouse, whereas the BTBR female mice did not show a preference. The second experiment examined whether the subject mouse preferred a stranger mouse or bedding from the stranger mouse home cage. Male BTBR mice always preferred bedding, whereas the C57BL/6J male mice did not show a preference. Both BTBR and C57BL/6J female mice preferred bedding when the stranger mouse was a different strain but not when the stranger mouse was the same strain. Therefore, the stranger mouse strain seems to influence the preference of the female mice more than the male mice. The mice preferred spending time in the chamber with the social smell but not the actual stranger mouse although not always significantly. This suggests that contact with a stranger mouse is more stressful or anxiety provoking than the smell. Autism Res 2019, 12: 1184-1191. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: BTBR T+ Itpr3tf /J (BTBR) mice have been used as a model of autism spectrum disorder (ASD) due to their low levels of sociability and high levels of repetitive grooming. These experiments explored social behavior in the BTBR and C57BL/6J mice using variations of the three-chambered social approach test. These experiments examined how the sociability level of the stranger mouse affected the subject mouse's preference and if social odor was preferable to a social situation in the BTBR mice. The BTBR male mice demonstrated a strong preference for the more social C57BL/6J stranger mouse, as did the C57BL/6J male mice. The C57BL/6J female mice showed a moderate preference for the BTBR stranger mouse, whereas the BTBR female mice did not show a preference for either stranger mouse. The second modification let the subject mouse have a choice between a stranger mouse or bedding. Male BTBR mice preferred bedding, regardless of the strain of the stranger mouse, whereas the C57BL/6J male mice did not show a preference. Both BTBR and C57BL/6J female mice preferred bedding when the stranger mouse was a different strain but showed no preference when the stranger mouse was from the same strain. The stranger mouse strain seems to influence the female mice more. Male BTBR mice preferred spending time in the chamber with the social smell but not the actual mouse, suggesting that actual contact with a stranger mouse is more stressful or anxiety provoking.