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Generation and characterisation of a parkin-Pacrg knockout mouse line and a Pacrg knockout mouse line
Mutations in PARK2 (parkin) can result in Parkinson’s disease (PD). Parkin shares a bidirectional promoter with parkin coregulated gene (PACRG) and the transcriptional start sites are separated by only ~200 bp. Bidirectionally regulated genes have been shown to function in common biological pathways...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951884/ https://www.ncbi.nlm.nih.gov/pubmed/29760428 http://dx.doi.org/10.1038/s41598-018-25766-1 |
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author | Stephenson, Sarah E. M. Aumann, Timothy D. Taylor, Juliet M. Riseley, Jessica R. Li, Ruili Mann, Jeffrey R. Tomas, Doris Lockhart, Paul J. |
author_facet | Stephenson, Sarah E. M. Aumann, Timothy D. Taylor, Juliet M. Riseley, Jessica R. Li, Ruili Mann, Jeffrey R. Tomas, Doris Lockhart, Paul J. |
author_sort | Stephenson, Sarah E. M. |
collection | PubMed |
description | Mutations in PARK2 (parkin) can result in Parkinson’s disease (PD). Parkin shares a bidirectional promoter with parkin coregulated gene (PACRG) and the transcriptional start sites are separated by only ~200 bp. Bidirectionally regulated genes have been shown to function in common biological pathways. Mice lacking parkin have largely failed to recapitulate the dopaminergic neuronal loss and movement impairments seen in individuals with parkin-mediated PD. We aimed to investigate the function of PACRG and test the hypothesis that parkin and PACRG function in a common pathway by generating and characterizing two novel knockout mouse lines harbouring loss of both parkin and Pacrg or Pacrg alone. Successful modification of the targeted allele was confirmed at the genomic, transcriptional and steady state protein levels for both genes. At 18–20 months of age, there were no significant differences in the behaviour of parental and mutant lines when assessed by openfield, rotarod and balance beam. Subsequent neuropathological examination suggested there was no gross abnormality of the dopaminergic system in the substantia nigra and no significant difference in the number of dopaminergic neurons in either knockout model compared to wildtype mice. |
format | Online Article Text |
id | pubmed-5951884 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59518842018-05-21 Generation and characterisation of a parkin-Pacrg knockout mouse line and a Pacrg knockout mouse line Stephenson, Sarah E. M. Aumann, Timothy D. Taylor, Juliet M. Riseley, Jessica R. Li, Ruili Mann, Jeffrey R. Tomas, Doris Lockhart, Paul J. Sci Rep Article Mutations in PARK2 (parkin) can result in Parkinson’s disease (PD). Parkin shares a bidirectional promoter with parkin coregulated gene (PACRG) and the transcriptional start sites are separated by only ~200 bp. Bidirectionally regulated genes have been shown to function in common biological pathways. Mice lacking parkin have largely failed to recapitulate the dopaminergic neuronal loss and movement impairments seen in individuals with parkin-mediated PD. We aimed to investigate the function of PACRG and test the hypothesis that parkin and PACRG function in a common pathway by generating and characterizing two novel knockout mouse lines harbouring loss of both parkin and Pacrg or Pacrg alone. Successful modification of the targeted allele was confirmed at the genomic, transcriptional and steady state protein levels for both genes. At 18–20 months of age, there were no significant differences in the behaviour of parental and mutant lines when assessed by openfield, rotarod and balance beam. Subsequent neuropathological examination suggested there was no gross abnormality of the dopaminergic system in the substantia nigra and no significant difference in the number of dopaminergic neurons in either knockout model compared to wildtype mice. Nature Publishing Group UK 2018-05-14 /pmc/articles/PMC5951884/ /pubmed/29760428 http://dx.doi.org/10.1038/s41598-018-25766-1 Text en © The Author(s) 2018 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Stephenson, Sarah E. M. Aumann, Timothy D. Taylor, Juliet M. Riseley, Jessica R. Li, Ruili Mann, Jeffrey R. Tomas, Doris Lockhart, Paul J. Generation and characterisation of a parkin-Pacrg knockout mouse line and a Pacrg knockout mouse line |
title | Generation and characterisation of a parkin-Pacrg knockout mouse line and a Pacrg knockout mouse line |
title_full | Generation and characterisation of a parkin-Pacrg knockout mouse line and a Pacrg knockout mouse line |
title_fullStr | Generation and characterisation of a parkin-Pacrg knockout mouse line and a Pacrg knockout mouse line |
title_full_unstemmed | Generation and characterisation of a parkin-Pacrg knockout mouse line and a Pacrg knockout mouse line |
title_short | Generation and characterisation of a parkin-Pacrg knockout mouse line and a Pacrg knockout mouse line |
title_sort | generation and characterisation of a parkin-pacrg knockout mouse line and a pacrg knockout mouse line |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951884/ https://www.ncbi.nlm.nih.gov/pubmed/29760428 http://dx.doi.org/10.1038/s41598-018-25766-1 |
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