Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease caused by mutations in the dystrophin gene, resulting in muscle degeneration and a shortened life expectancy. DMD patients have a higher prevalence of intellectual disability, anxiety, and autism spectrum disorder than the general population. The presence of at least seven alternative promoters, two polyA addition sites and multiple alternative splicing results in several dystrophin isoforms with different expression patterns and roles. Mutations affecting only the full-length isoforms (Dp427) are linked to emotional behavioural problems including anxiety, depression, and hyperactivity in DMD patients. DMD mouse models, that carry a mutation affecting Dp427 isoforms display an enhanced fear response, increased anxiety- and depressive-like behaviours. We hypothesised that dystrophin isoforms have differential expression in different brain areas and their deficiency results in the comorbidities present in patients. We aimed to investigate the different dystrophin isoforms localisation in mouse brain and identify potential candidate dystrophin protein interactors in the mouse brain. We used mdx5cv and mdx52 mice lacking Dp427and both Dp427 and Dp140, respectively. Our results revealed that Dp427c expression is high in cortex, while Dp427p1 and Dp427p2 are highly expressed in the cerebellum. Mdx52 and mdx5cv mice have very low Dp427 transcript levels, due to the mRNA being partially transcribed, while neither of these mouse models expressed Dp427 protein. Mass spectrometry analysis indicated different proteins interactions with Dp427, Dp140 and Dp71 in different mouse brain regions. Thus, this newfound knowledge will address the molecular networks associated with emotional and cognitive comorbidities in DMD.