FK866 mechanism validation in Rag1-/- mice

Validation Score: 0.850 Price: $0.50 Inflammatory bowel disease Rag1-/- mice with DSS-induced colitis Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting NAMPT in Rag1-/- mice with DSS-induced colitis. Primary outcome: Anti-inflammatory efficacy in absence of adaptive immunity

Description

Mechanistic validation experiment using Rag1-/- mice (lacking mature T and B cells) to determine whether FK866's therapeutic effects are primarily mediated through innate immune cells rather than adaptive immunity. This experiment was crucial for establishing that FK866's anti-inflammatory effects are independent of T and B cell responses and are primarily mediated through altered monocyte/macrophage biology. The effectiveness of FK866 in Rag1-/- mice confirmed that the therapeutic mechanism involves direct modulation of innate immune cell function, particularly macrophage polarization, rather than effects on adaptive immune responses.

TARGET GENE
MODEL SYSTEM
Rag1-/- mice with DSS-induced colitis
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
NAD metabolism, innate immunity
SOURCE
extracted_from_pmid_28877980
PRIMARY OUTCOME
Anti-inflammatory efficacy in absence of adaptive immunity

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%) 0.850 composite

📖 Wiki Pages

NAMPT GenegeneNAMPT Proteinprotein

Protocol

DSS-induced colitis in Rag1-/- mice treated with FK866, assessment of inflammatory parameters and innate immune cell responses

Expected Outcomes

Maintained anti-inflammatory efficacy demonstrating innate immune mechanism

Success Criteria

Significant anti-inflammatory effects in the absence of T and B cells

Related Hypotheses (3)

TREM2 R47H Variant-Driven Metabolic Dysfunction as the Primary Trigger for Failed DAM Transition0.862
Metabolic NAD+ Salvage Pathway Enhancement Through NAMPT Overexpression0.745
NAD+ Salvage Pathway Optimization0.455

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