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Ermin deficiency leads to compromised myelin, inflammatory milieu, and susceptibility to demyelinating insult
Author(s) -
Ziaei Amin,
GarciaMiralles Marta,
Radulescu Carola I.,
Sidik Harwin,
Silvin Aymeric,
Bae HanGyu,
Bonnard Carine,
Yusof Nur Amirah Binte Mohammad,
Ferrari Bardile Costanza,
Tan Liang Juin,
Ng Alvin Yu Jin,
Tohari Sumanty,
Dehghani Leila,
Henry Lily,
Yeo Xin Yi,
Lee Sejin,
Venkatesh Byrappa,
Langley Sarah R.,
Shaygannejad Vahid,
Reversade Bruno,
Jung Sangyong,
Ginhoux Florent,
Pouladi Mahmoud A.
Publication year - 2022
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.13064
Subject(s) - myelin , white matter , multiple sclerosis , astrogliosis , oligodendrocyte , corpus callosum , biology , demyelinating disorder , inflammation , central nervous system , neuroscience , immunology , pathology , medicine , magnetic resonance imaging , radiology
Ermin is an actin‐binding protein found almost exclusively in the central nervous system (CNS) as a component of myelin sheaths. Although Ermin has been predicted to play a role in the formation and stability of myelin sheaths, this has not been directly examined in vivo. Here, we show that Ermin is essential for myelin sheath integrity and normal saltatory conduction. Loss of Ermin in mice caused de‐compacted and fragmented myelin sheaths and led to slower conduction along with progressive neurological deficits. RNA sequencing of the corpus callosum, the largest white matter structure in the CNS, pointed to inflammatory activation in aged Ermin‐deficient mice, which was corroborated by increased levels of microgliosis and astrogliosis. The inflammatory milieu and myelin abnormalities were further associated with increased susceptibility to immune‐mediated demyelination insult in Ermin knockout mice. Supporting a possible role of Ermin deficiency in inflammatory white matter disorders, a rare inactivating mutation in the ERMN gene was identified in multiple sclerosis patients. Our findings demonstrate a critical role for Ermin in maintaining myelin integrity. Given its near‐exclusive expression in myelinating oligodendrocytes, Ermin deficiency represents a compelling “inside‐out” model of inflammatory dysmyelination and may offer a new paradigm for the development of myelin stability‐targeted therapies.

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