A new model to study the brain disorders associated with Duchenne muscular dystrophy
The severity of cognitive and behavioral disturbances is variable in patients with Duchenne muscular dystrophy (DMD), which seems to depend on the position of the mutation within the dystrophin (DMD) gene. The exon52-deleted mdx52 mouse has been very little studied but is of major importance for understanding the brain dysfunctions in this disease. Indeed, its deletion is located in a hotspot region of the gene mutated in about 50% of patients, which impairs the expression of two brain dystrophins, Dp427 and Dp140.
Two French teams (C Vaillend, Paris-Saclay Institute of Neuroscience, in collaboration with A Goyenvalle, Université de Versailles St-Quentin-en-Yvelines) involved in the European consortium BIND (Brain INvolvement in Dystrophinopathies) have published a first characterization of this model in the journal DISEASE MODELS AND MECHANISMS. Using an in vivo magnetic resonance imaging approach (collaboration with CEA/SHFJ, BioMaps Paris-Saclay University) and neurohistology, the authors show the absence of major brain malformations in mdx52 mice, suggesting that the dysfunctions in this model are rather at a cellular level. They then show that mdx52 mice display a strong increase in anxiety and stress reactivity, and a major deficit in an associative learning task involving emotional responses. This phenotypic profile is reminiscent of the emotional disorders and internalization problems described in DMD patients. These robust phenotypes will be used in future preclinical studies to evakuate the efficacy of treatments targeting brain dysfunction in DMD.
Emotional behavior and brain anatomy of the mdx52 mouse model of Duchenne muscular dystrophy. Amel Saoudi, Faouzi Zarrouki, Catherine Sebrié, Charlotte Izabelle, Aurélie Goyenvalle, Cyrille Vaillend.
Article published in Disease Models & Mechanisms – Access to the manuscript
