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

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 phys...

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Autores principales: Gao, Yujing, Wilson, Gabrielle R., Stephenson, Sarah E. M., Oulad-Abdelghani, Mustapha, Charlet-Berguerand, Nicolas, Bozaoglu, Kiymet, McLean, Catriona A., Thomas, Paul Q., Finkelstein, David I., Lockhart, Paul J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106796/
https://www.ncbi.nlm.nih.gov/pubmed/32228644
http://dx.doi.org/10.1186/s13041-020-00584-7
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author Gao, Yujing
Wilson, Gabrielle R.
Stephenson, Sarah E. M.
Oulad-Abdelghani, Mustapha
Charlet-Berguerand, Nicolas
Bozaoglu, Kiymet
McLean, Catriona A.
Thomas, Paul Q.
Finkelstein, David I.
Lockhart, Paul J.
author_facet Gao, Yujing
Wilson, Gabrielle R.
Stephenson, Sarah E. M.
Oulad-Abdelghani, Mustapha
Charlet-Berguerand, Nicolas
Bozaoglu, Kiymet
McLean, Catriona A.
Thomas, Paul Q.
Finkelstein, David I.
Lockhart, Paul J.
author_sort Gao, Yujing
collection PubMed
description 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.
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spelling pubmed-71067962020-04-01 Distribution of Parkinson’s disease associated RAB39B in mouse brain tissue Gao, Yujing Wilson, Gabrielle R. Stephenson, Sarah E. M. Oulad-Abdelghani, Mustapha Charlet-Berguerand, Nicolas Bozaoglu, Kiymet McLean, Catriona A. Thomas, Paul Q. Finkelstein, David I. Lockhart, Paul J. Mol Brain Short Report 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. BioMed Central 2020-03-30 /pmc/articles/PMC7106796/ /pubmed/32228644 http://dx.doi.org/10.1186/s13041-020-00584-7 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Short Report
Gao, Yujing
Wilson, Gabrielle R.
Stephenson, Sarah E. M.
Oulad-Abdelghani, Mustapha
Charlet-Berguerand, Nicolas
Bozaoglu, Kiymet
McLean, Catriona A.
Thomas, Paul Q.
Finkelstein, David I.
Lockhart, Paul J.
Distribution of Parkinson’s disease associated RAB39B in mouse brain tissue
title Distribution of Parkinson’s disease associated RAB39B in mouse brain tissue
title_full Distribution of Parkinson’s disease associated RAB39B in mouse brain tissue
title_fullStr Distribution of Parkinson’s disease associated RAB39B in mouse brain tissue
title_full_unstemmed Distribution of Parkinson’s disease associated RAB39B in mouse brain tissue
title_short Distribution of Parkinson’s disease associated RAB39B in mouse brain tissue
title_sort distribution of parkinson’s disease associated rab39b in mouse brain tissue
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106796/
https://www.ncbi.nlm.nih.gov/pubmed/32228644
http://dx.doi.org/10.1186/s13041-020-00584-7
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