In the present study we also compared the BALB/cJ strain, a mouse model of pathological aggression, to BALB/cByJ controls, and found intronic variants in Foxp2 and one of its downstream targets, Cntnap2. Previous studies in human cellular models have shown that the protein encoded by FOXP2 can directly bind to regulatory regions in the CNTNAP2 locus to repress its expression [44]. Interestingly, mice with cortical-specific knockout of Foxp2 have been reported to show abnormalities in social behaviors [45]. Although these findings may indicate that the intronic SNVs are relevant to the behavioral differences between the strains, further evidence is needed to show that the variants actually have functional relevance for the mouse phenotype. Future studies may utilize complementary data comparing gene expression in the two mouse lines or could investigate functional impact (e.g., do they map to credible enhancer regions, are they likely to alter binding for transcription factors?) of the SNVs identified.
