{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T09:55:16Z","timestamp":1777888516367,"version":"3.51.4"},"reference-count":50,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPD"],"published-print":{"date-parts":[[2021,4,13]]},"abstract":"<jats:p>Background: Coding mutations in the LRRK2 gene, encoding for a large protein kinase, have been shown to cause familial Parkinson\u2019s disease (PD). The immediate biological consequence of LRRK2 mutations is to increase kinase activity, suggesting 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. Objective: Considering the evidence for interactions between LRRK2 and RAB29 on the genetic and protein levels, we set out to determine whether there are any consequences on brain function with aging after deletion of both genes. Methods: We generated a double knockout mouse model and performed a battery of motor and non-motor behavioral tests. We then investigated postmortem assays to determine the presence of PD-like pathology, including nigral dopamine cell count, astrogliosis, microgliosis, and striatal monoamine content. Results: Behaviorally, we noted only that 18\u201324-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 the outcomes that represented PD-like pathology. Conclusion: 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.<\/jats:p>","DOI":"10.3233\/jpd-202172","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T12:21:46Z","timestamp":1611922906000},"page":"569-584","source":"Crossref","is-referenced-by-count":7,"title":["Combined Knockout of Lrrk2 and Rab29 Does Not Result in Behavioral Abnormalities in vivo"],"prefix":"10.1177","volume":"11","author":[{"given":"Melissa Conti","family":"Mazza","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"},{"name":"Howard University, Washington, DC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Beilina","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ema","family":"Karakoleva","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Coyle","sequence":"additional","affiliation":[{"name":"Behavioral Neuroscience Program, Department of Psychology, Binghamton University, Binghamton, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhui","family":"Ding","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, 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