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). Parkinshares a bidirectional promoter with parkincoregulated 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 parkinhave largely failed to recapitulate the dopaminergicneuronal loss and movement impairments seen in individuals with parkin-mediated PD. We aimed to investigate the function of PACRG and test the hypothesis that parkinand PACRG function in a common pathway by generating and characterizing two novel knockout mouselines harbouring loss of both parkinand 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 dopaminergicsystem in the substantia nigra and no significant difference in the number of dopaminergicneurons in either knockout model compared to wildtype mice.