Striatum Proteomics from LacQ140 mutant Huntingtin lowering mouse model

ABSTRACT: Lowering of mutant Huntingtin (mHtt) transcript and protein levels is considered a therapeutic strategy for people with Huntington’s disease (HD). However, the effects of mHtt lowering are incompletely understood. In this study, the proteomic changes in striatum upon Htt lowering were analyzed, using an inducible HD-knock-in LacQ140 mouse model with temporal control of mHtt-Q140 expression. The proteomic HD-disease signature in LacQ140 mouse striata was defined, using label-free quantification by liquid chromatography-mass spectrometry in data-independent acquisition mode. From the over 8000 protein groups identified in the striata, a disease signature of differentially regulated proteins in LacQ140 mice was identified, compared to wildtype control mice at 2-, 6-, 9- and 12-months of age. The effect of mHtt lowering on striatal proteomics was explored in LacQ140 mice, in which mHtt was lowered by repressing its transcription starting at an early or late time point, before or after onset of behavioral, molecular and aggregation phenotypes.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Huntington Disease

SUBMITTER: Frank Rolfs  

LAB HEAD: Christoph Schaab

PROVIDER: PXD054495 | Pride | 2025-04-11

REPOSITORIES: pride