Defects in myelination, paranode organization and Purkinje cell innervation in the ether lipid-deficient mouse cerebellum
Open accessAbstract
Ether lipids (ELs), particularly plasmalogens, are essential constituents of the mammalian central nervous system. The physiological role of ELs, in vivo, however is still enigmatic. In the present study, we characterized a mouse model carrying a targeted deletion of the peroxisomal dihydroxyacetonephosphate acyltransferase gene that results in the complete lack of ELs. Investigating the cerebellum of these mice, we observed: (i) defects in foliation patterning and delay in precursor granule cell migration, (ii) defects in myelination and concomitant reduction in the level of myelin basic protein, (iii) disturbances in paranode organization by extending the Caspr distribution and disrupting axo-glial septate-like junctions, (iv) impaired innervation of Purkinje cells by both parallel fibers and climbing fibers and (v) formation of axon swellings by the accumulation of inositol-tris-phosphate receptor 1 containing smooth ER-like tubuli. Functionally, conduction velocity of myelinated axons in the corpus callosum was significantly reduced. Most of these phenotypes were already apparent at P20 but still persisted in 1-year-old animals. In summary, these data show that EL deficiency results in severe developmental and lasting structural alterations at the cellular and network level of the cerebellum, and reveal an important role of ELs for proper brain function. Common molecular mechanisms that may underlie these phenotypes are discussed.
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Foliation defects with underdevelopment of fissures, particularly foliae VI and VII, occur in Gnpat KO mice.
“Concordantly, foliation defects with underdevelopment of fissures, particularly affecting foliae VI and VII, have been reported in Gnpat KO mice at different postnatal stages [218,225].”
From Peroxisomes in brain development and function (2016) · cites this paper as [218]
Hypomyelination in cerebellum and cortical areas of Gnpat KO mice is accompanied by changes in nodes of Ranvier architecture causing delayed action potential propagation.
“Furthermore, hypomyelination in cerebellum (and also in cortical areas) of Gnpat KO mice was accompanied by changes in the architecture of the nodes of Ranvier resulting in a delay in the propagation of action potentials [218].”
From Peroxisomes in brain development and function (2016) · cites this paper as [218]
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- Authors
- Teigler, A., Komljenovic, D., Draguhn, A., Gorgas, K., & Just, W. W.
- Affiliations
- Heidelberg University (DE)
- Corresponding author
- Just, Wilhelm W.
- ORCID
- Draguhn, Andreas
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-03-08
- Volume
- 18
- Issue
- 11
- Pages
- 1897-1908
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC2722228
- OpenAlex
- W2164666271
- Cited by
- 99
- References
- 81
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 3 · 2023: 8 · 2022: 7 · 2021: 5 · 2020: 7 · 2019: 6 · 2018: 3 · 2017: 5 · 2016: 4 · 2015: 5 · 2014: 7 · 2013: 4 · 2012: 13
- FWCI
- 3.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P01CA095616)
- National Institute of Neurological Disorders and Stroke (U24NS050606)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- ether lipids, plasmalogens, DAP12, cerebellum, myelination, myelin basic protein, Caspr, parallel fibers, climbing fibers, axonal swellings, smooth endoplasmic reticulum, granule cell migration, axonal myelination
- MeSH terms
- Acyltransferases, Animals, Axons, Cell Movement, Cerebellum, Myelin Basic Protein, Intercellular Junctions, Kidney, Myelin Sheath, Phospholipid Ethers, Purkinje Cells, Mice, Knockout, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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