Dmd mdx mice have defective oligodendrogenesis, delayed myelin compaction and persistent hypomyelination

Author:

Arreguin Andrea J.12ORCID,Shao Zijian1,Colognato Holly1ORCID

Affiliation:

1. Stony Brook University 1 Department of Pharmacological Sciences , , Stony Brook, NY 11794 , USA

2. Stony Brook University 2 Medical Scientist Training Program (MSTP) , , Stony Brook, NY 11794-8651 , USA

Abstract

ABSTRACT Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene, resulting in the loss of dystrophin, a large cytosolic protein that links the cytoskeleton to extracellular matrix receptors in skeletal muscle. Aside from progressive muscle damage, many patients with DMD also have neurological deficits of unknown etiology. To investigate potential mechanisms for DMD neurological deficits, we assessed postnatal oligodendrogenesis and myelination in the Dmdmdx mouse model. In the ventricular-subventricular zone (V-SVZ) stem cell niche, we found that oligodendrocyte progenitor cell (OPC) production was deficient, with reduced OPC densities and proliferation, despite a normal stem cell niche organization. In the Dmdmdx corpus callosum, a large white matter tract adjacent to the V-SVZ, we also observed reduced OPC proliferation and fewer oligodendrocytes. Transmission electron microscopy further revealed significantly thinner myelin, an increased number of abnormal myelin structures and delayed myelin compaction, with hypomyelination persisting into adulthood. Our findings reveal alterations in oligodendrocyte development and myelination that support the hypothesis that changes in diffusion tensor imaging seen in patients with DMD reflect developmental changes in myelin architecture.

Funder

National Institutes of Health

Department of Defense CDMRP

Stony Brook University

Publisher

The Company of Biologists

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