Myelin and Lipid Composition of the Corpus Callosum in Mucopolysaccharidosis Type I Mice

Steven Q. Le, Igor Nestrasil, Shih hsin Kan, Martin Egeland, Jonathan D. Cooper, David Elashoff, Rong Guo, Jakub Tolar, Jennifer K. Yee, Patricia I. Dickson

Research output: Contribution to journalArticlepeer-review

Abstract

Mucopolysaccharidosis type I (MPS I) is a lysosomal disease with progressive central nervous system involvement. This study examined the lipid, cholesterol, and myelin basic protein composition of white matter in the corpus callosum of MPS I mice. We studied 50 week-old, male MPS I mice and littermate, heterozygote controls (n = 12 per group). Male MPS I mice showed lower phosphatidylcholine and ether-linked phosphatidylcholine quantities than controls (p < 0.05). Twenty-two phospholipid or ceramide species showed significant differences in percent of total. Regarding specific lipid species, MPS I mice exhibited lower quantities of sphingomyelin 18:1, phosphatidylserine 38:3, and hexosylceramide d18:1(22:1) mH2O than controls. Principal components analyses of polar, ceramide, and hexosylceramide lipids, respectively, showed some separation of MPS I and control mice. We found no significant differences in myelin gene expression, myelin basic protein, or total cholesterol in the MPS I mice versus heterozygous controls. There was a trend toward lower proteolipid protein-1 levels in MPS I mice (p = 0.06). MPS I mice show subtle changes in white matter composition, with an unknown impact on pathogenesis in this model.

Original languageEnglish (US)
Pages (from-to)627-637
Number of pages11
JournalLipids
Volume55
Issue number6
DOIs
StatePublished - Nov 2020

Bibliographical note

Funding Information:
We would like to thank Ron McElmurry for the brain harvesting and shipment. Research was supported by R01 NS085381 to P.I.D. S.‐h.K. was supported by a T32 fellowship in the UCLA Medical Genetics Training Program (GM008243). The Center for Magnetic Resonance Research at the University of Minnesota is supported by P41 EB015894 and P30 NS076408. The lipid analyses described in this work were performed at the Kansas Lipidomics Research Center Analytical Laboratory. Instrument acquisition and lipidomics method development was supported by National Science Foundation (EPS 0236913, MCB 1413036, DBI 0521587, DBI1228622), Kansas Technology Enterprise Corporation, K‐IDeA Networks of Biomedical Research Excellence (INBRE) of National Institute of Health (P20GM103418), and Kansas State University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors report the following conflicts of interest: research/grant support from BioMarin Pharmaceutical and/or Sanofi Genzyme, which manufacture and distribute enzyme replacement therapy for mucopolysaccharidosis type I.

Funding Information:
We would like to thank Ron McElmurry for the brain harvesting and shipment. Research was supported by R01 NS085381 to P.I.D. S.-h.K. was supported by a T32 fellowship in the UCLA Medical Genetics Training Program (GM008243). The Center for Magnetic Resonance Research at the University of Minnesota is supported by P41 EB015894 and P30 NS076408. The lipid analyses described in this work were performed at the Kansas Lipidomics Research Center Analytical Laboratory. Instrument acquisition and lipidomics method development was supported by National Science Foundation (EPS 0236913, MCB 1413036, DBI 0521587, DBI1228622), Kansas Technology Enterprise Corporation, K-IDeA Networks of Biomedical Research Excellence (INBRE) of National Institute of Health (P20GM103418), and Kansas State University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors report the following conflicts of interest: research/grant support from BioMarin Pharmaceutical and/or Sanofi Genzyme, which manufacture and distribute enzyme replacement therapy for mucopolysaccharidosis type I. The authors declare that they have no conflict of interest.

Publisher Copyright:
© 2020 AOCS

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

  • Glycosaminoglycans
  • Hurler syndrome
  • Inborn errors of metabolism
  • Lipidomics
  • Lysosomal storage disease

PubMed: MeSH publication types

  • Journal Article
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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