Journal article

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

Sarah EM Stephenson, Timothy D Aumann, Juliet M Taylor, Jessica R Riseley, Ruili Li, Jeffrey R Mann, Doris Tomas, Paul J Lockhart

SCIENTIFIC REPORTS | NATURE PUBLISHING GROUP | Published : 2018

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...

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Grants

Awarded by National Health and Medical Research Council Australia


Funding Acknowledgements

The C57BL/6 J mouse strain expressing both the Cre recombinase gene (Gt(ROSA)26Sor-TgPGKCre) and the FLP1 recombinase gene (Tg(ACTFLPe)9205Dym) was a kind gift from Professor Robert Brink at the Garvin Institute of Medical Research (GIMR). We thank Dr Cattram Nguyen for statistical advice. This work was supported in part by the National Health and Medical Research Council Australia (https://www.nhmrc.gov.au/) GNT1046206 to PJL. Additional infrastructure funding to the Murdoch Children's Research Institute was provided by the Australian Government National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme (https://www.nhmrc.gov.au/) and the Victorian Government's Operational Infrastructure Support Program (https://www.vic.gov.au/). SS and PJL were supported by National Health and Medical Research Council Australia post graduate scholarship (Id 491311) and Career Development Fellowship (GNT1032364), respectively.