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

Bauke Kogelman; Artem Khmelinskii; Ingrid Verhaart; Laura van Vliet; Diewertje I Bink; Annemieke Aartsma-Rus; Maaike van Putten; Louise van der Weerd

doi:10.1371/journal.pone.0194636

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

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

Authors

Bauke Kogelman¹, Artem Khmelinskii^{2

3}, Ingrid Verhaart⁴, Laura van Vliet⁴, Diewertje I Bink^{1

5}, Annemieke Aartsma-Rus⁴, Maaike van Putten⁴, Louise van der Weerd^{1

4}

Affiliations

¹ Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
² Division of Image Processing, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
³ Percuros B.V., Enschede, the Netherlands.
⁴ Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
⁵ Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / pathology*
Disease Models, Animal
Dystrophin / metabolism*
Female
Male
Mice
Muscular Dystrophy, Duchenne / metabolism*
Muscular Dystrophy, Duchenne / pathology*
Organ Size

Substances

Dystrophin

Associated data

Dryad/10.5061/dryad.7s2dq

Grants and funding

BK was supported European Union Bioimage-NMD project (http://www.bioimage-nmd.eu), Seventh Framework Programme (FP7/2007-2013) under grant 602485. AK was supported by Percuros B.V. by the FP7 European Union Marie Curie IAPP Program, BRAINPATH (http://www.brainpath.eu), under grant 612360. The funder Percuros B.V. provided support in the form of salaries for author AK, but did not, as all other funders, have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.