P2rx7 congenic mouse model insulin tolerance testing

Validation Score: 0.900 Price: $0.50 insulin resistance congenic mice (C57BL6 P2rx7 allele on 129SvJ background) Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting P2rx7 in congenic mice (C57BL6 P2rx7 allele on 129SvJ background). Primary outcome: insulin sensitivity

Description

Insulin tolerance testing was performed on the same congenic mouse model system to assess insulin sensitivity in P2x7-C57 versus P2x7-129 mice. This experiment complemented the glucose tolerance testing by specifically examining insulin responsiveness. The P2x7-C57 mice carrying the hypomorphic P2rx7 allele showed reduced insulin sensitivity compared to P2x7-129 mice, demonstrating that P2X7 dysfunction affects both glucose tolerance and insulin responsiveness. This provided comprehensive characterization of the glucose homeostasis phenotype in the P2rx7 hypomorphic model.

TARGET GENE
P2rx7
MODEL SYSTEM
congenic mice (C57BL6 P2rx7 allele on 129SvJ background)
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
purinergic signaling
SOURCE
extracted_from_pmid_25719930
PRIMARY OUTCOME
insulin sensitivity

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

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Protocol

Protocol: P2rx7 Congenic Mouse Model Insulin Tolerance Testing

Study Design


Metabolic characterization of P2rx7 congenic mice (C57BL/6J P2rx7 allele on 129SvJ background) to assess the impact of P2X7 receptor variation on insulin sensitivity and glucose homeostasis.

Animals and Breeding

  • Congenic mice: C57BL/6J-P2rx7 allele introgressed onto 129SvJ background (N≥10 generations)
  • Control: 129SvJ background mice with endogenous P2rx7
  • Groups:
    • Male and female P2rx7 congenic (n=10-12 per sex)
    • Age-matched 129SvJ controls (n=10-12 per sex)
    4. Age: 10-12 weeks (young adult) for initial metabolic phenotyping
  • Optional: aged cohort (24 weeks) if young mice show no phenotype
  • ...

    Expected Outcomes

    Expected Outcomes

    Primary Outcomes

  • Impaired insulin sensitivity: P2rx7 congenic mice show 20-40% higher glucose AUC during ITT vs 129SvJ controls
  • Altered IL-1β: P2X7 variation may affect NLRP3 inflammasome activation and IL-1β release
  • Tissue-specific P2rx7 expression: Higher expression in immune cells, adipose tissue vs muscle
  • Secondary Outcomes

    • Fasting insulin levels may differ between genotypes
    • Body weight and fat mass differences possible
    • Lipid profile alterations (triglycerides, free fatty acids)

    ...

    Success Criteria

    Success Criteria

    Primary

    • [ ] ≥8 animals/group complete ITT with full 120-min glucose curve
    • [ ] Baseline glucose similar between groups (no significant difference)
    • [ ] Control mice show ≥30% glucose reduction from baseline (assay validity)
    • [ ] Glucose AUC significantly different between congenic and control (p < 0.05)

    Secondary

    • [ ] P2rx7 expression confirmed in WAT, muscle, liver by qPCR
    • [ ] Terminal insulin measured (fasting state)
    • [ ] Inflammatory markers (IL-1β, IL-6) quantified in plasma

    ...

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