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

Scientific Reports
Sarah E M StephensonPaul J Lockhart

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 wildt...Continue Reading

References

Dec 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·P D BurbeloY Yamada
Sep 24, 1999·The Journal of Cell Biology·R García-MataE S Sztul
May 8, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·A CiechanoverA L Schwartz
May 29, 2000·The New England Journal of Medicine·C B LückingUNKNOWN European Consortium on Genetic Susceptibility in Parkinson's Disease
Aug 31, 2001·Biochemical and Biophysical Research Communications·S AsakawaN Shimizu
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jan 28, 2003·Journal of Molecular Biology·Andrew B WestMatthew J Farrer
Mar 12, 2003·Neurology·T ForoudUNKNOWN Parkinson Study Group
Mar 28, 2003·The Journal of Biological Chemistry·Steven M TownsonSteffi Oesterreich
Sep 16, 2003·The Journal of Biological Chemistry·Aaron C PawlykVirginia M-Y Lee
Jan 27, 2004·Movement Disorders : Official Journal of the Movement Disorder Society·Paul J LockhartMatthew J Farrer
Feb 21, 2004·Human Molecular Genetics·Ignacio F MataMatthew J Farrer
Mar 12, 2004·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Diego LorenzettiMonica Justice
May 19, 2004·Proceedings of the National Academy of Sciences of the United States of America·Diego LorenzettiMonica J Justice
Jun 21, 2005·Current Biology : CB·Lani C KellerWallace F Marshall
Jul 8, 2005·Movement Disorders : Official Journal of the Movement Disorder Society·Jason D Dapper, Monica J Justice
Nov 3, 2006·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Jian Feng
Nov 3, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lixia ZhaoYue Feng
Sep 6, 2007·Journal of Neuroscience Research·Carol Anne Chénard, Stéphane Richard
Apr 23, 2008·Current Protocols in Neuroscience·R J CarterS B Dunnett
Nov 28, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Qian JiangJian Feng
Feb 7, 2009·Parkinsonism & Related Disorders·Juliet M TaylorPaul J Lockhart
Mar 10, 2009·Fertility and Sterility·Gabrielle R WilsonPaul J Lockhart
Nov 18, 2009·Journal of Neuropathology and Experimental Neurology·Yun Ju C SongTamas R Revesz
Jan 22, 2010·Journal of Neurochemistry·Chenere P Ramsey, Benoit I Giasson
Apr 28, 2010·Molecular Neurodegeneration·Hongyu WangIlya Bezprozvanny
Sep 21, 2013·Annual Review of Pharmacology and Toxicology·Samuel M Goldman
Feb 8, 2014·Ageing Research Reviews·Amy ReeveDoug Turnbull
Mar 19, 2014·Parkinsonism & Related Disorders·Raja MehannaEugene C Lai
Apr 17, 2014·Trends in Neurosciences·Leslie A ScarffeTed M Dawson
Feb 5, 2015·Journal of Visualized Experiments : JoVE·Doris TomasTim D Aumann

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Citations

Jan 18, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·Yujing GaoPaul J Lockhart
Apr 2, 2020·Molecular Brain·Yujing GaoPaul J Lockhart
Feb 6, 2020·Science Signaling·Jens MeschedeKonstanze F Winklhofer
Nov 11, 2020·Acta Neuropathologica Communications·Peter M J QuinnC Henrique Alves
Jan 6, 2021·Cellular and Molecular Neurobiology·Dhanya KrishnanSrinivas Gopala

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Methods Mentioned

BETA
ubiquitination
transmission electron microscopy
PCR
transgenic
genotyping
phosphotransferase
electrophoresis
Protein Assay

Software Mentioned

AnyMaze
ImageQuant TL
Rota rod CUB
GraphPad Prism
Kinovea

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