Impact of distinct dystrophin gene mutations on behavioral phenotypes of Duchenne muscular dystrophy

The severity of brain comorbidities in Duchenne muscular dystrophy (DMD) depends on the mutation position within the DMD gene and differential loss of distinct brain dystrophin isoforms (i.e. Dp427, Dp140, Dp71). Comparative studies of DMD mouse models with different mutation profiles may help to un...

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Bibliographic Details
Published in:Disease models & mechanisms 2024-12, Vol.17 (12)
Main Authors: Saoudi, Amel, Mitsogiannis, Manuela D, Zarrouki, Faouzi, Fergus, Claire, Stojek, Erwina, Talavera, Silvia, Moore-Frederick, Dervla, Kelly, Vincent P, Goyenvalle, Aurélie, Montanaro, Federica, Muntoni, Francesco, Prenderville, Jack A, Sokolowska, Ewa, Vaillend, Cyrille
Format: Article
Language:English
Subjects:
Animals
Anxiety - genetics
Behavior, Animal
Disease Models, Animal
Dystrophin - genetics
Fear
Male
Mice
Mice, Inbred C57BL
Mice, Inbred mdx
Muscular Dystrophy, Duchenne - genetics
Muscular Dystrophy, Duchenne - pathology
Mutation - genetics
Phenotype
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Summary:The severity of brain comorbidities in Duchenne muscular dystrophy (DMD) depends on the mutation position within the DMD gene and differential loss of distinct brain dystrophin isoforms (i.e. Dp427, Dp140, Dp71). Comparative studies of DMD mouse models with different mutation profiles may help to understand this genotype-phenotype relationship. The aim of this study was (1) to compare the phenotypes due to Dp427 loss in mdx5cv mice to those of mdx52 mice, which concomitantly lack Dp427 and Dp140; and (2) to evaluate replicability of phenotypes in separate laboratories. We show that mdx5cv mice displayed impaired fear conditioning and robust anxiety-related responses, the severity of which was higher in mdx52 mice. Depression-related phenotypes presented variably in these models and were difficult to replicate between laboratories. Recognition memory was unaltered or minimally affected in mdx5cv and mdx52 mice, at variance with the cognitive deficits described in the original Dp427-deficient mdx mouse, suggesting a difference related to its distinct genetic background. Our results confirm that Dp140 loss may increase the severity of emotional disturbances, and provide insights on the limits of the reproducibility of behavioral studies in DMD mouse models.
ISSN:1754-8411
1754-8411
DOI:10.1242/dmm.050707