Longitudinal TLR2 reporter gene study in α-synuclein mice

Validation Score: 0.900 Price: $0.50 Parkinson's disease Thy1.2-α-synuclein transgenic mice with TLR2 reporter construct Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting TLR2, SNCA in Thy1.2-α-synuclein transgenic mice with TLR2 reporter construct. Primary outcome: TLR2 promoter activity over time

Description

A longitudinal bioluminescence imaging study was conducted using Thy1.2-α-synuclein transgenic mice that expressed a bicistronic DNA construct containing reporter genes (luciferase and green fluorescent protein) under the transcriptional control of the murine toll-like receptor 2 promoter. Monthly imaging revealed progressive increases in TLR2 expression starting from 10 months of age. This experiment provided real-time monitoring of TLR2 activation over time in living animals with α-synuclein pathology, demonstrating that α-synuclein overexpression leads to a progressive microglial response and TLR2 upregulation with age-dependent onset.

TARGET GENE
TLR2, SNCA
MODEL SYSTEM
Thy1.2-α-synuclein transgenic mice with TLR2 reporter construct
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
toll-like receptor 2 signaling, microglial activation
SOURCE
extracted_from_pmid_25522431
PRIMARY OUTCOME
TLR2 promoter activity over time

Scoring Dimensions

Info Gain 0.00 (25%) Feasibility 0.00 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.00 (10%) Ethical Safety 0.00 (10%) 0.900 composite

📖 Wiki Pages

TLR2 Protein — Toll-Like Receptor 2proteinTLR2 — Toll-Like Receptor 2geneSNCA→Alpha-synuclein→Parkinson's Disease Causal Chpathwaysnca-proteinproteinSNCA — Alpha-SynucleingeneSNCA — Alpha-Synuclein Gene Entity PagegeneSNCA A53TdiseaseSNCA→Alpha-synuclein→Aggregation→Lewy Bodies→SynucpathwaySNCA-Overexpressing Dopaminergic NeuronscellSNCA-A53T Alpha-Synuclein NeuronscellSNCA Gene Variants and MutationsdiseaseDNA Damage Repair Deficiency Validation Study in PexperimentDNA Damage Response in Corticobasal SyndromemechanismDNA MethylationentityDepression in Neurodegenerationdisease

Protocol

Monthly bioluminescence imaging using luciferase reporter under TLR2 promoter control

Expected Outcomes

Progressive increase in TLR2 expression with age

Success Criteria

Detectable bioluminescence signal increase over time

Related Hypotheses (1)

Neuronal Subtype-Specific Alpha-Synuclein Expression Normalization0.571

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