The homozygous LRRK2.p.N1437D point mutation mouse is a novel model of parkinsonism.

ABSTRACT: The leucine-rich repeat kinase 2 (LRRK2) gene is one of the most common genetic causes of autosomal dominant Parkinson's disease (PD) and a common genetic risk factor for sporadic PD. However, aged mice with common LRRK2 point mutations fail to exhibit age-related PD-associated behavioral and pathological impairments. We generated a novel mouse model harboring the LRRK2.p.N1437D point mutation (c.4309 A > G; NM_98578). Here, the homozygous N1437D mutation, but not the heterozygous mutation, led to an increase in the autophosphorylation, substrate phosphorylation, and GTP-binding capacity of LRRK2. Heterozygous N1437D mice also showed unaffected behavior and pathology while the homozygous mice exhibited PD-associated behavioral change at 25-26 months, dopamine system damage, lipofuscin accu

SUBMITTER: Gan LH 

PROVIDER: S-EPMC11953335 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature