Affective phenotypes in heterozygous <i>LRRK2</i> R1441G knock-in mice.

ABSTRACT: Several missense mutations in the LRRK2 gene are linked to familial Parkinson's disease (PD). Although LRRK2 mutant mouse models typically lack gross motor impairments, their contribution to non-motor PD symptoms remains largely underexplored. In this study, we showed that the R1441G missense mutation promoted behavioural despair in the forced swim test (FST) and led to anhedonia, reflected in reduced sucrose preference, while the typical expression of helplessness in avoidance learning, induced by undermining locus of control, was unaffected. Notably, these depressive phenotypes emerged predominantly in heterozygous R1441G knock-in (KI) mice, and a similar dominant negative phenotype was evident in the elevated plus maze, with heterozygous mutants exhibiting lower anxiety th

SUBMITTER: Ng MHF 

PROVIDER: S-EPMC12426193 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature