Duchenne muscular dystrophy (DMD) is a serious genetic condition that causes muscles to weaken and break down over time. While it mainly affects muscle strength, many people with DMD also experience learning and behaviour challenges. These brain-related issues are thought to be linked to the loss of certain versions (isoforms) of a protein called dystrophin, which is present not only in muscle but also in the brain. To better understand how the deficiency of these dystrophin isoforms in the brain leads to behavioural issues, we studied where they are normally present in the brain during different stages of development in healthy mice.

We found that different types of brain regions use different dystrophin isoforms. Some isoforms, named Dp140 and Dp71, change a lot during brain development, suggesting they play specific roles in early brain formation. Another isoform named Dp71, was the most common isoform in the adult brain. We also looked at two types of mouse models used to study DMD. These mice had misspelling in the dystrophin gene similar to those seen in people with DMD, and as expected, they lacked certain dystrophin isoforms in the brain. This study is the first to map when and where each of these brain dystrophin isoforms are found in mice. It gives researchers a better understanding of how the loss of dystrophin might lead to brain and behaviour problems in DMD patients.