The presence and severity of learning weaknesses and behavioural disturbances is highly variable among patients affected by Duchenne muscular dystrophy (DMD), which is believed to depend on the position of the mutation within the dystrophin (DMD) gene. The exon-52-deleted mdx52 mouse is a critical model of DMD, as it features a deletion in a hotspot region of the DMD gene. This means the gene mutation is relatively common in people affected by DMD.
Deletion of exon 52 hinders the expression of several brain dystrophins. For this reason, this provides a key model for studying the cognitive impairment that are linked to DMD and testing rescuing strategies.
The findings of the French BIND partner groups (Dr C Vaillend, Paris-Saclay Institute of Neuroscience – Centre National de la Recherche Scientifique, in collaboration with A Goyenvalle, laboratory Biothérapies des Maladies Neuromusculaires, Université de Versailles St-Quentin-en-Yvelines) are now published in the journal Disease Models and Mechanisms.
Amel Saoudi, Faouzi Zarrouki, Catherine Sebrié, Charlotte Izabelle, Aurélie Goyenvalle, Cyrille Vaillend. Emotional behavior and brain anatomy of the mdx52 mouse model of Duchenne muscular dystrophy. Dis Model Mech, 1 September 2021; 14 (9): dmm049028. doi: https://doi.org/10.1242/dmm.049028
Researchers from this paper first present brain images obtained from in vivo magnetic resonance imaging (MRI in live mice) and neurohistology (microscopic analyses of brain regions) and conclude that there are no large brain abnormalities or malformations in the mdx52 mice. This suggests that the neural dysfunctions in this model are likely at the level of brain cell functions.
Then, they investigated emotional behaviour and emotional learning, comparing to mice with a different mutation and to unaffected mice. They found that mdx52 mice showed more anxiety and fear in response to stress, and a severe impairment in a type of associative learning involving emotional responses.
Importantly, these outcomes can be replicated and seem comparable to the emotional and behavioural problems that are reported in a quarter of people living with DMD. These behavioural phenotypes will therefore be used in future comparative preclinical studies to estimate the efficacy of treatments that are targeting brain dysfunctions in DMD.
About the BIND project
The BIND project addresses the characterisation of brain involvement in Duchenne and Becker Muscular Dystrophy (DMD and BMD), a previously overlooked field. The aims of this EU-funded project connecting 19 partners is to:
- better understand brain regions that express dystrophin and their function;
- identify brain comorbidities that could be corrected with a postnatal treatment intervention;
- define the spectrum of brain comorbidities in DMD and BMD individuals, and how to best assess them;
- and create optimal and uniform outcome measures to assess brain comorbidities in DMD/BMD.