Endothelium-specific TBK1 knockdown in atherosclerosis model

Validation Score: 0.900 Price: $0.50 atherosclerosis endothelium-specific TBK1 knockdown mice Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting TBK1 in endothelium-specific TBK1 knockdown mice. Primary outcome: effect of TBK1 knockdown on EndMT and plaque formation

Description

Endothelium-specific TBK1 knockdown mice were generated and used to investigate the role of TBK1 in endothelial-to-mesenchymal transition and atherogenesis. The study examined the effects of reducing TBK1 expression specifically in endothelial cells on atherosclerotic plaque formation and endothelial dysfunction. This genetic approach allowed for tissue-specific investigation of TBK1's role while avoiding systemic effects that might confound results.

TARGET GENE
TBK1
MODEL SYSTEM
endothelium-specific TBK1 knockdown mice
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
endothelial-to-mesenchymal transition, atherogenesis
SOURCE
extracted_from_pmid_41685426
PRIMARY OUTCOME
effect of TBK1 knockdown on EndMT and plaque formation

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

TBK1 Protein (TANK-Binding Kinase 1)proteinTBK1-Mediated Neuroinflammation Hypothesis — ImpaimechanismTBK1 ProteinproteinTBK1 Autophagy and Neuroinflammation ALS/FTD CausamechanismTBK1-Mediated Neuroinflammation Hypothesis — AutophypothesisTBK1 — TANK Binding Kinase 1geneTBK1 GenegeneEndothelial CellscellcGAS-STING Inhibitor Therapy for NeurodegenerationtherapeuticXenophagy in NeurodegenerationmechanismTREM2 in Frontotemporal DementiamechanismTREM2 in Amyotrophic Lateral SclerosismechanismTDP-43 RNA Granule PathwaymechanismAdvanced Proteolysis and Ubiquitin System TargetinmechanismPINK1-Parkin Mitophagy Complexpathway

Protocol

endothelium-specific genetic knockdown of TBK1

Expected Outcomes

reduced EndMT and atherosclerotic plaque formation

Success Criteria

decreased endothelial dysfunction and plaque burden compared to controls

Related Hypotheses (1)

TBK1 Loss-of-Function Amplifies C1q-Mediated Synapse Elimination Through Type I IFN Hyperactivation0.520

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