The behavioural consequences of dystrophinopathy
Minou A T Verhaeg, Elizabeth M van Der Pijl, Davy can de Vijver, Christa L Tanganyika-de Winter, Tiberiu L Stan, Angel van Uffelen, Luciano Censoni, Maaike can Putten. The behavioural consequences of dystrophinopathy. Disease Models & Mechanisms. 2025, 18 (2).
Lay Summary
Duchenne muscular dystrophy (DMD) is a severe disorder caused by mutations in the DMD gene which prevent expression of dystrophin protein. Dystrophin is not only present in muscle, but several unique dystrophin proteins, differing in size (Dp427, Dp140 Dp71/40), are also found in the brain. Depending on the position of the mutation, DMD patients lack one or multiple different dystrophin proteins. Lack of Dp427 dystrophin in the brain results in behavioural and cognitive problems and these become more severe when also Dp140 or all dystrophin proteins are missing.
To gain a better understanding of the consequences of the lack of one, several or all of the brain dystrophin proteins, we assessed behaviour in several DMD mouse models site by site. The findings confirm that the absence of Dp427 makes mice more anxious and fearful. The additional loss of Dp140 did not further exacerbate this, but was shown to influence spontaneous behaviour, such as how mice react to changes in their environment, like light/dark switches. Additionally, the study highlights the role of Dp71/Dp40 isoforms in regulating behaviours related to anxiety and spontaneous activity. This research provides new insights into the complex relationship between the brain dystrophin proteins and behavioural impairments in DMD, offering a more detailed understanding of the disorder’s cognitive and emotional impacts. This knowledge will be helpful for future experiments aimed to address these behavioural alterations.
