Generation and characterisation of a parkin-Pacrg knockout mouse line and a Pacrg knockout mouse line
AuthorStephenson, SEM; Aumann, TD; Taylor, JM; Riseley, JR; Li, R; Mann, JR; Tomas, D; Lockhart, PJ
Source TitleScientific Reports
PublisherNATURE PUBLISHING GROUP
University of Melbourne Author/sTaylor, Juliet; Aumann, Timothy; Lockhart, Paul; Li, Ruili; Stephenson, Sarah; Tomas, Doris
Florey Department of Neuroscience and Mental Health
Pharmacology and Therapeutics
Document TypeJournal Article
CitationsStephenson, S. E. M., Aumann, T. D., Taylor, J. M., Riseley, J. R., Li, R., Mann, J. R., Tomas, D. & Lockhart, P. J. (2018). Generation and characterisation of a parkin-Pacrg knockout mouse line and a Pacrg knockout mouse line. SCIENTIFIC REPORTS, 8 (1), https://doi.org/10.1038/s41598-018-25766-1.
Access StatusOpen Access
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.
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