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Most of the patients are characterized by early\u2010onset cerebral demyelination with apoptotic oligodendrocyte (OL) death and die before 2\u00a0years of age. However, the mechanisms of molecular pathogenesis in the developing OLs before death and the exact causes of white matter degeneration remain largely unknown. We have recently reported that OLs of twitcher mouse, an authentic mouse model of KD, exhibit developmental defects and endogenous accumulation of psychosine (galactosylsphingosine), a cytotoxic lyso\u2010derivative of galactosylceramide. Here, we show that attenuated expression of microRNA (miR)\u2010219, a critical regulator of OL differentiation and myelination, mediates cellular pathogenesis of KD OLs. Expression and functional activity of miR\u2010219 were repressed in developing twitcher mouse OLs. By using OL precursor cells (OPCs) isolated from the twitcher mouse brain, we show that exogenously supplemented miR\u2010219 effectively rescued their cell\u2010autonomous developmental defects and apoptotic death. miR\u2010219 also reduced endogenous accumulation of psychosine in twitcher OLs. Collectively, these results highlight the role of the reduced miR\u2010219 expression in KD pathogenesis and suggest that miR\u2010219\u00a0has therapeutic potential for treating KD OL pathologies.<\/jats:p>","DOI":"10.1111\/bpa.12951","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T13:49:46Z","timestamp":1617716986000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Reduction in miR\u2010219 expression underlies cellular pathogenesis of oligodendrocytes in a mouse model of Krabbe disease"],"prefix":"10.1111","volume":"31","author":[{"given":"Naoko","family":"Inamura","sequence":"first","affiliation":[{"name":"Department of Cellular Pathology, Institute for Developmental Research Aichi Developmental Disability Center Kasugai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Go","sequence":"additional","affiliation":[{"name":"Department of 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