Distribution of Parkinson's disease associated RAB39B in mouse brain tissue

Yujing Gao, Gabrielle R. Wilson, Sarah E.M. Stephenson, Mustapha Oulad-Abdelghani, Nicolas Charlet-Berguerand, Kiymet Bozaoglu, Catriona A. McLean, Paul Q. Thomas, David I. Finkelstein, Paul J. Lockhart

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Pathogenic variants in the gene encoding the small GTPase Ras analogue in Brain 39b (RAB39B) are associated with early-onset parkinsonism. In this study we investigated the expression and localization of RAB39B (RNA and protein) in mouse brain tissue to gain a better understanding of its normal physiological function(s) and role in disease. We developed novel resources, including monoclonal antibodies directed against RAB39B and mice with Rab39b knockout, and performed real-time PCR and western blot analysis on whole brain lysates. To determine the spatial localization of Rab39b RNA and protein, we performed in-situ hybridization and immunohistochemistry on fresh frozen and fixed brain tissue. Our results show that RAB39B is localized throughout the cortex, hippocampus and substantia nigra of mice throughout postnatal life. We found high levels of RAB39B within MAP2 positive cortical and hippocampal neurons, and TH positive dopaminergic neurons in the substantia nigra pars compacta. Our studies support and extend current knowledge of the localization of RAB39B. We validate RAB39B as a neuron-enriched protein and demonstrate that it is present throughout the mouse cortex and hippocampus. Further, we observe high levels in the substantia nigra pars compacta, the brain region most affected in Parkinson's disease pathology. The distribution of Rab39b is consistent with human disease associations with parkinsonism and cognitive impairment. We also describe and validate novel resources, including monoclonal antibodies directed against RAB39B and mice with Rab39b knockout, both of which are valuable tools for future studies of the molecular function of RAB39B.

Original languageEnglish
Article number52
JournalMolecular brain
Volume13
Issue number1
DOIs
Publication statusPublished - 30 Mar 2020
Externally publishedYes

Keywords

  • Knockout mouse
  • Mouse model
  • Parkinson's disease
  • Parkinsonism
  • Protein localization
  • RAB GTPase
  • RAB39B

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Gao, Y., Wilson, G. R., Stephenson, S. E. M., Oulad-Abdelghani, M., Charlet-Berguerand, N., Bozaoglu, K., ... Lockhart, P. J. (2020). Distribution of Parkinson's disease associated RAB39B in mouse brain tissue. Molecular brain, 13(1), [52]. https://doi.org/10.1186/s13041-020-00584-7