Quantitative Microproteomics Based Characterization of the Central and Peripheral Nervous System of a Mouse Model of Krabbe Disease

Mol Cell Proteomics. 2019 Jun;18(6):1227-1241. doi: 10.1074/mcp.RA118.001267. Epub 2019 Mar 29.


Krabbe disease is a rare, childhood lysosomal storage disorder caused by a deficiency of galactosylceramide beta-galactosidase (GALC). The major effect of GALC deficiency is the accumulation of psychosine in the nervous system and widespread degeneration of oligodendrocytes and Schwann cells, causing rapid demyelination. The molecular mechanisms of Krabbe disease are not yet fully elucidated and a definite cure is still missing. Here we report the first in-depth characterization of the proteome of the Twitcher mouse, a spontaneous mouse model of Krabbe disease, to investigate the proteome changes in the Central and Peripheral Nervous System. We applied a TMT-based workflow to compare the proteomes of the corpus callosum, motor cortex and sciatic nerves of littermate homozygous Twitcher and wild-type mice. More than 400 protein groups exhibited differences in expression and included proteins involved in pathways that can be linked to Krabbe disease, such as inflammatory and defense response, lysosomal proteins accumulation, demyelination, reduced nervous system development and cell adhesion. These findings provide new insights on the molecular mechanisms of Krabbe disease, representing a starting point for future functional experiments to study the molecular pathogenesis of Krabbe disease. Data are available via ProteomeXchange with identifier PXD010594.

Keywords: Autophagy; Inflammation; Mass Spectrometry; Mouse models; Neurobiology*; Neurodegenerative diseases*; Pathway Analysis; Protein Identification*; Quantification; TMT labeling; laser capture microdissection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System / metabolism*
  • Central Nervous System / pathology
  • Disease Models, Animal
  • Female
  • Gene Ontology
  • Leukodystrophy, Globoid Cell / metabolism*
  • Male
  • Mice
  • Peripheral Nervous System / metabolism*
  • Peripheral Nervous System / pathology
  • Principal Component Analysis
  • Proteome / metabolism
  • Proteomics / methods*


  • Proteome