| First Author | Mazza MC | Year | 2020 |
| Journal | bioRxiv | Mgi Jnum | J:314235 |
| Mgi Id | MGI:6818633 | Doi | 10.1101/2020.05.13.093708 |
| Citation | Mazza MC, et al. (2020) Combined knockout of Lrrk2 and Rab29 does not result in behavioral abnormalities in vivo. bioRxiv |
| abstractText | Coding mutations in the LRRK2 gene, encoding for a large protein kinase, have been shown to cause familial Parkinsonâs disease (PD). The immediate biological consequence of LRRK2 mutations is to increase kinase activity, leading to the suggestion that inhibition of this enzyme might be useful therapeutically to slow disease progression. Genome-wide association studies have identified the chromosomal loci around LRRK2 and one of its proposed substrates, RAB29, as contributors towards the lifetime risk of sporadic PD. Considering the evidence for interactions between LRRK2 and RAB29 on the genetic and protein levels, here we generated a double knockout mouse model and determined whether there are any consequences on brain function with aging. From a battery of motor and non-motor behavioral tests, we noted only that 18-24 month Rab29-/- and double (Lrrk2-/-/Rab29-/-) knockout mice had diminished locomotor behavior in open field compared to wildtype mice. However, no genotype differences were seen in number of substantia nigra pars compacta (SNc) dopamine neurons or in tyrosine hydroxylase levels in the SNc and striatum, which might reflect a PD-like pathology. These results suggest that depletion of both Lrrk2 and Rab29 is tolerated, at least in mice, and support that this pathway might be able to be safely targeted for therapeutics in humans. |
