Amel Saoudi, Manuela D. Mitsogiannis, Faouzi Zarrouki, Claire Fergus, Erwina Stoke, Silvia Talavera, Dervla Moore-Frederick, Vincent P Kelly, Aurélie Goyenvalle, Federica Montanaro, Francesco Muntoni, Jack A Prenderville, Ewa Sokolowska, Cyrille Vaillend. Impact of distinct dystrophin gene mutations on behavioural phenotypes of Duchenne Muscular Dystrophy. Disease Models & Mechanisms. 2024, 17 (12).

https://journals.biologists.com/dmm/article/17/12/dmm050707/364863/Impact-of-distinct-dystrophin-gene-mutations-onhttps://www.nature.com/articles/s41467-025-56644-w

In Duchenne muscular dystrophy (DMD), the severity of brain-related challenges can vary depending on where the genetic mutation occurs. This is because different mutations affect different dystrophin proteins, which are important for brain function. The proteins Dp427, Dp140, and Dp71 play key roles in emotions, memory, and behaviour. To better understand how the loss of these proteins affects behaviour, researchers compared two types of genetically modified mice with DMD-like mutations. 

One group of mice (mdx5cv) was missing the Dp427 protein, while the other group (mdx52) lacked both Dp427 and Dp140. The researchers found that both types of mice showed signs of anxiety and fear, but the mice missing both proteins had more severe symptoms. Interestingly, signs of depression were harder to measure and often varied depending on the laboratory, suggesting that these behaviours may be influenced by environmental factors or testing conditions. On the other hand, memory problems were either mild or absent in both mouse models, which differed from earlier research on other types of DMD mice.

These findings suggest that losing Dp140 may worsen emotional difficulties in DMD. The study also highlights the challenges of replicating behavioural experiments across different labs, emphasizing the need for careful consideration when comparing results. Ultimately, this research helps scientists to better understand how genetic mutations in DMD contribute to brain-related symptoms.