Generation and characterisation of a parkin-Pacrg knockout mouse line and a Pacrg knockout mouse line

Abstract 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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sarah E. M. Stephenson, Timothy D. Aumann, Juliet M. Taylor, Jessica R. Riseley, Ruili Li, Jeffrey R. Mann, Doris Tomas, Paul J. Lockhart
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7a0bdeea927949b1a7ff3473d4e57c33
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7a0bdeea927949b1a7ff3473d4e57c33
record_format	dspace
spelling	oai:doaj.org-article:7a0bdeea927949b1a7ff3473d4e57c332021-12-02T15:08:22ZGeneration and characterisation of a parkin-Pacrg knockout mouse line and a Pacrg knockout mouse line10.1038/s41598-018-25766-12045-2322https://doaj.org/article/7a0bdeea927949b1a7ff3473d4e57c332018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25766-1https://doaj.org/toc/2045-2322Abstract 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.Sarah E. M. StephensonTimothy D. AumannJuliet M. TaylorJessica R. RiseleyRuili LiJeffrey R. MannDoris TomasPaul J. LockhartNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarah E. M. Stephenson Timothy D. Aumann Juliet M. Taylor Jessica R. Riseley Ruili Li Jeffrey R. Mann Doris Tomas Paul J. Lockhart Generation and characterisation of a parkin-Pacrg knockout mouse line and a Pacrg knockout mouse line
description	Abstract 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	article
author	Sarah E. M. Stephenson Timothy D. Aumann Juliet M. Taylor Jessica R. Riseley Ruili Li Jeffrey R. Mann Doris Tomas Paul J. Lockhart
author_facet	Sarah E. M. Stephenson Timothy D. Aumann Juliet M. Taylor Jessica R. Riseley Ruili Li Jeffrey R. Mann Doris Tomas Paul J. Lockhart
author_sort	Sarah E. M. Stephenson
title	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_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_sort	generation and characterisation of a parkin-pacrg knockout mouse line and a pacrg knockout mouse line
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/7a0bdeea927949b1a7ff3473d4e57c33
work_keys_str_mv	AT sarahemstephenson generationandcharacterisationofaparkinpacrgknockoutmouselineandapacrgknockoutmouseline AT timothydaumann generationandcharacterisationofaparkinpacrgknockoutmouselineandapacrgknockoutmouseline AT julietmtaylor generationandcharacterisationofaparkinpacrgknockoutmouselineandapacrgknockoutmouseline AT jessicarriseley generationandcharacterisationofaparkinpacrgknockoutmouselineandapacrgknockoutmouseline AT ruilili generationandcharacterisationofaparkinpacrgknockoutmouselineandapacrgknockoutmouseline AT jeffreyrmann generationandcharacterisationofaparkinpacrgknockoutmouselineandapacrgknockoutmouseline AT doristomas generationandcharacterisationofaparkinpacrgknockoutmouselineandapacrgknockoutmouseline AT pauljlockhart generationandcharacterisationofaparkinpacrgknockoutmouselineandapacrgknockoutmouseline
_version_	1718388195524083712

Generation and characterisation of a parkin-Pacrg knockout mouse line and a Pacrg knockout mouse line

Ejemplares similares