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Proteome of R1441C and G2019S LRRK2 knock in mice after striatal motor learning task

ABSTRACT: LRRK2 mutations are associated with both familial and sporadic forms of Parkinson’s disease (PD). Convergent evidence suggests that LRRK2 plays critical roles in regulating striatal function. Here, by using knock-in mouse lines that express the two most common LRRK2 pathogenic mutations—G2019S and R1441C—we investigated how pathogenic LRRK2 mutations altered striatal physiology. To identify the signaling pathways that underlie the motor learning deficits, specifically in the RC mice we performed six-plex tandem mass tag (TMT) quantitative mass spectrometry (MS) to compare the protein expression of either RC or GS and WT mice following the five days of the rotarod test.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Parkinson's Disease

SUBMITTER: Renu Goel

LAB HEAD: Loukia Parisiadou

PROVIDER: PXD037003 | Pride | 2022-12-15

REPOSITORIES: Pride

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R1441C and G2019S LRRK2 knockin mice have distinct striatal molecular, physiological, and behavioral alterations.

Xenias Harry S HS Chen Chuyu C Kang Shuo S Cherian Suraj S Situ Xiaolei X Shanmugasundaram Bharanidharan B Liu Guoxiang G Scesa Giuseppe G Savio Chan C C Parisiadou Loukia L

Communications biology 20221110 1

LRRK2 mutations are closely associated with Parkinson's disease (PD). Convergent evidence suggests that LRRK2 regulates striatal function. Here, by using knock-in mouse lines expressing the two most common LRRK2 pathogenic mutations-G2019S and R1441C-we investigated how LRRK2 mutations altered striatal physiology. While we found that both R1441C and G2019S mice displayed reduced nigrostriatal dopamine release, hypoexcitability in indirect-pathway striatal projection neurons, and alterations asso ...[more]

PMID: 36357506

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