ac0c01933_si_001.pdf (437.59 kB)
Download fileUnequivocal Mapping of Molecular Ether Lipid Species by LC–MS/MS in Plasmalogen-Deficient Mice
journal contribution
posted on 07.08.2020, 15:04 authored by Jakob Koch, Katharina Lackner, Yvonne Wohlfarter, Sabrina Sailer, Johannes Zschocke, Ernst R. Werner, Katrin Watschinger, Markus A. KellerDeficient
ether lipid biosynthesis in rhizomelic chondrodysplasia
punctata and other disorders is associated with a wide range of severe
symptoms including small stature with proximal shortening of the limbs,
contractures, facial dysmorphism, congenital cataracts, ichthyosis,
spasticity, microcephaly, and mental disability. Mouse models are
available but show less severe symptoms. In both humans and mice,
it has remained elusive which of the symptoms can be attributed to
lack of plasmanyl or plasmenyl ether lipids. The latter compounds,
better known as plasmalogens, harbor a vinyl ether double bond conferring
special chemical and physical properties. Discrimination between plasmanyl
and plasmenyl ether lipids is a major analytical challenge, especially
in complex lipid extracts with many isobaric species. Consequently,
these lipids are often neglected also in recent lipidomic studies.
Here, we present a comprehensive LC–MS/MS based approach that
allows unequivocal distinction of these two lipid subclasses based
on their chromatographic properties. The method was validated using
a novel plasmalogen-deficient mouse model, which lacks plasmanylethanolamine
desaturase and therefore cannot form plasmenyl ether lipids. We demonstrate
that plasmanylethanolamine desaturase deficiency causes an accumulation
of plasmanyl species, a too little studied but biologically important
substance class.
History
Usage metrics
Read the peer-reviewed publication
Categories
Keywords
Plasmalogen-Deficient Mice Deficien...plasmenyl ether lipidslipid subclassesrhizomelic chondrodysplasia punctatavinyl etherplasmanylethanolamine desaturase de...Unequivocal Mappingplasmanylethanolamine desaturasemouse modelsplasmanyl specieslipid extractslatter compoundsMolecular Ether Lipid SpeciessymptomLCisobaric speciesnovel plasmalogen-deficient mouse modellipidomic studiessubstance class