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. 2018 Mar 30;13(3):e0194636.
doi: 10.1371/journal.pone.0194636. eCollection 2018.

Influence of full-length dystrophin on brain volumes in mouse models of Duchenne muscular dystrophy

Bauke Kogelman  1 , Artem Khmelinskii  2   3 , Ingrid Verhaart  4 , Laura van Vliet  4 , Diewertje I Bink  1   5 , Annemieke Aartsma-Rus  4 , Maaike van Putten  4 , Louise van der Weerd  1   4
Affiliations

Influence of full-length dystrophin on brain volumes in mouse models of Duchenne muscular dystrophy

Bauke Kogelman et al. PLoS One. .

Abstract

Duchenne muscular dystrophy (DMD) affects besides muscle also the brain, resulting in memory and behavioral problems. The consequences of dystrophinopathy on gross macroscopic alterations are unclear. To elucidate the effect of full-length dystrophin expression on brain morphology, we used high-resolution post-mortem MRI in mouse models that either express 0% (mdx), 100% (BL10) or a low amount of full-length dystrophin (mdx-XistΔhs). While absence or low amounts of full-length dystrophin did not significantly affect whole brain volume and skull morphology, we found differences in volume of individual brain structures. The results are in line with observations in humans, where whole brain volume was found to be reduced only in patients lacking both full-length dystrophin and the shorter isoform Dp140.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Dystrophin expression in mdx-XistΔhs mice.
A: Representative Western blot of mdx-XistΔhs brains revealed that mice expressed low levels of full-length dystrophin in their brain. Levels varied between individuals but were below 20% in all mice. Post Synaptic Density Protein 95 (Psdp95) served as a loading control. Wildtype samples for the concentration series were diluted in mdx protein lysate to ensure equal protein loading of all samples. B: mRNA expression levels of neither full-length nor Dp71 differed between mdx and BL10 mice. However, expression of Dp427c was higher in BL10 compared to mdx-XistΔhs mice. Error bars represents the standard deviation. Asterisk indicates P<0.05.
Fig 2
Fig 2. The volumes of 22 segmented brain structures in mdx, BL10, mdx-XistΔhs and BL10-XistΔhs mice were compared within each genetic background (mdx vs BL10 and mdx-XistΔhs vs BL10-XistΔhs).
The brain structures found significantly different in volume after false discovery rate correction are shown and consisted of both grey and white matter structures for both comparisons. Coronal, sagittal and axial planes are shown indicated by white lines. A: Comparison between mdx and BL10 showed four different brain structures: the hippocampus, globus pallidus, caudate putamen and hypothalamus. B: Comparison between mdx-XistΔhs and BL10-XistΔhs showed 13 different structures.
See this image and copyright information in PMC

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