CERS2 genetic deletion rescues IL-10 deficiency inflammation

Validation Score: 0.850 Price: $0.50 inflammatory bowel disease IL-10/CERS2 double knockout mice Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting CERS2 in IL-10/CERS2 double knockout mice. Primary outcome: Inflammatory gene expression levels and disease severity

Description

Genetic deletion study of ceramide synthase 2 (Cers2) to test whether removing the enzyme responsible for VLC ceramide production could limit the inflammatory gene expression program associated with IL-10 deficiency. This experiment involved creating double knockout mice lacking both IL-10 and CERS2 to determine if blocking VLC ceramide synthesis could rescue the inflammatory phenotype.

TARGET GENE
MODEL SYSTEM
IL-10/CERS2 double knockout mice
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
VLC ceramide synthesis pathway, sphingolipid metabolism
SOURCE
extracted_from_pmid_38383790
PRIMARY OUTCOME
Inflammatory gene expression levels and disease severity

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

CERS2 Protein (Ceramide Synthase 2)proteinCERS2 — Ceramide Synthase 2 (Lass2)geneCerebellar Interneurons in NeurodegenerationcellMedial Forebrain Bundle in NeurodegenerationcellVentral Tegmental Area Dopamine Neurons in NeurodecellProtein Aggregation SeedingmechanismMedial Nucleus of the Trapezoid Body (MNTB) NeuroncellER Stress and UPR Modulator Therapy for NeurodegentherapeuticTrapezoid Body ComplexcellLateral Superior Olive (LSO) Neuronscell

Protocol

Generation of Cers2 knockout mice on IL-10 deficient background, assessment of inflammatory gene expression both in vitro and in vivo

Expected Outcomes

CERS2 deletion limits exacerbated inflammatory gene expression in IL-10 deficient mice

Success Criteria

Reduced inflammatory gene expression and improved disease phenotype in double knockout mice

Related Hypotheses (1)

Sphingolipid Metabolism Reprogramming0.663

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