Social deficits in BTBR T + tf/J mice are unchanged by cross‐fostering with C57BL/6J mothers

Inbred strains of mice are useful model systems for studying the interactions of genetic and environmental contributions during neurodevelopmental stages. We recently reported an inbred strain, BTBR T + tf/J (BTBR), which, as compared to the commonly used C57BL/6J (B6) strain, displays lower social interactions as juveniles, lower social approach in adult ages, and higher levels of repetitive self‐grooming throughout developmental stages. The present study investigated whether the early postnatal maternal environment contributes substantially to the unusually low expression of social behaviors and high self‐grooming in BTBR as compared to B6. Within 24 h of birth, entire litters of pups were cross‐fostered to either a dam of the same strain or a dam of the opposite strain. Control litters were left with their own mothers. Offspring were tested for juvenile play at postnatal day 21 ± 1, for sociability at 8 weeks of age in an automated three‐chambered social approach test, and for self‐grooming at 9–11 weeks of age. Results indicate that deficits in play behaviors in juvenile BTBR pups were not rescued by a B6 maternal environment. Similarly, a BTBR maternal environment did not induce play deficits in B6 pups. Cross‐fostering had no effect on sociability scores in adults. The high self‐grooming in BTBR and low self‐grooming in B6 were not affected by maternal environment. These findings favor a genetic interpretation of the unusual social behaviors and self‐grooming traits of BTBR, and support the use of the BTBR inbred strain as a mouse model to study genetic mechanism of autism.