Social deficits, stereotypy and early emergence of repetitive behavior in the C58/J inbred mouse strain

Abstract

Mouse lines with behavioral phenotypes relevant to symptoms in neurodevelopmental disorders may provide models to test hypotheses about disease etiology and to evaluate potential treatments. The present studies were designed to confirm and expand earlier work on the intriguing behavioral profile of the C58/J inbred strain, including low social approach and aberrant repetitive movements. Additional tests were selected to reflect aspects of autism, a severe neurodevelopmental disorder characterized by emergence of symptoms early in life, higher prevalence in males, social deficits and abnormal repetitive behavior. Mice from the C57BL/6J inbred strain, which has a similar genetic lineage and physical appearance to C58/J, served as a comparison group. Our results revealed that C58/J mice display elevated activity levels by postnatal day 6, which persist into adulthood. Despite normal olfactory ability, young adult male C58/J mice showed deficits in social approach in the three-chambered choice assay and failed to demonstrate social transmission of food preference. In contrast, female C58/J mice performed similarly to female C57BL/6J mice in both social tests. C58/J mice of both sexes demonstrated abnormal repetitive behaviors, displaying excessive jumping and back flipping in both social and non-social situations. These stereotypies were clearly evident in C58/J pups by postnatal days 20-21, and were also observed in C58/J dams during a test for maternal behavior. Overall, the strain profile for C58/J, including spontaneously developing motor stereotypies emerging early in the developmental trajectory, and social deficits primarily in males, models multiple components of the autism phenotype.

Fig 1. Maternal behavior in C57 and C58 dams

Measures were taken during a 15-min test in a clean cage containing the dam and litter. Data shown are mean + SEM for 11 C57 and 6 C58 dams. Post-hoc tests were not conducted for (B), due to zero scores for the C57 dams. * p<0.05.

Fig 2. Pup responses during the maternal behavior test

Measures were taken during a 15-min test in a clean housing cage containing the dam and litter. Data shown are mean + SEM for 11 C57 and 6 C58 litters. Data are missing for one C57 litter and 2 C58 litters for the measure of “Leaves Pup Huddle.” Post-hoc tests were not conducted for “Upright-Scrabbling”, due to zero scores for the C57 pups. * p<0.05.

Fig 3. Time spent sniffing the cotton swab in the olfactory habituation/dishabituation assay

No significant differences between the two strains were found for either sex. Data shown are mean ± SEM.

Fig 4. Social approach in a three-chambered choice task

Measures taken were time in each side and time spent sniffing each wire cage during tests for sociability (upper panels) and preference for social novelty (lower panels). Significant strain differences in social approach were only observed in the male groups (upper panels, lower right panel). Data shown are mean + SEM for each 10-min test. # p<0.05, across-strain comparison with same measure in same-sex mice. * p<0.05, within-group comparison, stranger 1 side different from opposite side.

Fig 5. The amount of food eaten and the number of eating bouts in a social transmission of food preference assay

Male C57BL/6J mice, but not male C58/J mice, had significant preference for the target food. No strain effects were found in the female groups. Data shown are mean + SEM for a 1-hr test. * p < 0.05 vs. within-strain comparison, target vs. non-target food.