Genetic ablation of Gpnmb does not alter synuclein-related pathology

Neurobiol Dis. 2021 Nov:159:105494. doi: 10.1016/j.nbd.2021.105494. Epub 2021 Aug 28.

Abstract

The gene GPNMB is known to play roles in phagocytosis and tissue repair, and is upregulated in microglia in many mouse models of neurodegenerative disease as well as in human patients. Nearby genomic variants are associated with both elevated Parkinson's disease (PD) risk and higher expression of this gene, suggesting that inhibiting GPNMB activity might be protective in Parkinson's disease. We tested this hypothesis in three different mouse models of neurological diseases: a remyelination model and two models of alpha-synuclein pathology. We found that Gpnmb deletion had no effect on histological, cellular, behavioral, neurochemical or gene expression phenotypes in any of these models. These data suggest that Gpnmb does not play a major role in the development of pathology or functional defects in these models and that further work is necessary to study its role in the development or progression of Parkinson's disease.

Keywords: Alpha synuclein; GPNMB; Genetics; Parkinson's disease; Phagocytosis; eQTL.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Eye Proteins / genetics*
  • Female
  • Humans
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Knockout
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Remyelination / genetics*
  • Substantia Nigra / metabolism*
  • Substantia Nigra / pathology
  • Synucleinopathies / genetics*
  • Synucleinopathies / metabolism
  • Synucleinopathies / pathology

Substances

  • Eye Proteins
  • GPNMB protein, human
  • Gpnmb protein, mouse
  • Membrane Glycoproteins