{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gan LH"],"funding":["China Postdoctoral Science Foundation","National Natural Science Foundation of China (National Science Foundation of China)"],"pagination":["61"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11953335"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(1)"],"pubmed_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"],"journal":["NPJ Parkinson's disease"],"pubmed_title":["The homozygous LRRK2.p.N1437D point mutation mouse is a novel model of parkinsonism."],"pmcid":["PMC11953335"],"funding_grant_id":["2022M710742","92249302","82371261","82201406","82171421","82271511","82371432"],"pubmed_authors":["Qi ZY","Tang YL","Yu WB","Zhou XY","Gan LH","Liu FT","Sun YM","Xiao BG","Wang J","Wu JJ"],"additional_accession":[]},"is_claimable":false,"name":"The homozygous LRRK2.p.N1437D point mutation mouse is a novel model of parkinsonism.","description":"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","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2025-06-25T03:04:29.227Z","creation":"2025-06-25T03:04:29.227Z"},"accession":"S-EPMC11953335","cross_references":{"pubmed":["40155632"],"doi":["10.1038/s41531-025-00905-4"]}}