Inbred strain preference in the BTBR T+ Itpr3tf /J mouse model of autism spectrum disorder: Does the stranger mouse matter in social approach?
BTBR males like social smell yet dodge the stranger mouse, so add an odor-only trial when you test social drugs.
01Research in Context
What this study did
Ryan et al. (2019) ran three-chamber social tests with BTBR mice. These mice are bred to show autism-like traits. The team asked: does the strain of the stranger mouse change how much the test mouse approaches?
They put a male or female BTBR mouse in the middle chamber. On one side they placed a wire cup with a stranger mouse. On the other side they put just the stranger’s bedding scent. They tried three stranger strains: C57, BALB, and another BTBR.
What they found
Male BTBR mice picked the scent side every time. They avoided the stranger mouse even while they liked the social smell. Female BTBR mice switched choices depending on who the stranger was. With a C57 stranger they spent more time with the mouse. With another BTBR they stayed near the scent only.
In short, strain and odor both steer social approach. A simple “social vs. empty” score can hide these twists.
How this fits with other research
Capio et al. (2013) used the same three-chamber test with Fmr1 knockout mice. They also saw that small changes—like raising mice alone—shift social choices. Both papers warn: run the test the same way each time or you will get mixed results.
Reynolds et al. (2013) studied BTBR mice too, but looked at repetitive grooming. They found enrichment cut grooming time in half yet kept the behavior rigid. Together with KatieLynne’s work, it shows BTBR mice can look “better” on one measure while still acting odd on another.
Ellegood et al. (2011) mapped brain volume in a different autism model (NL3 knock-in). Their mice had white-matter loss but no social test was run. Pairing their brain data with KatieLynne’s behavior data hints that social oddities can arise through different neural routes.
Why it matters
If you use BTBR mice to screen drugs for social deficits, add an odor-only condition. A treatment might boost scent approach while the mouse still avoids contact. Track both measures so you don’t miss hidden effects. Share the stranger strain in your methods so others can copy your setup and build clear evidence.
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02At a glance
03Original abstract
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.
Autism research : official journal of the International Society for Autism Research, 2019 · doi:10.1002/aur.2158