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Optic nerve myelination analysis

Exploratory Score: 0.880 Price: $0.50 optic atrophy Gabra1+/-/Gabrg2+/- mice Status: proposed

What This Experiment Tests

Exploratory experiment designed to discover new patterns targeting Gabra1, Gabrg2 in Gabra1+/-/Gabrg2+/- mice. Primary outcome: G-ratio of optic nerve axons

Description

Electron microscopy analysis of optic nerve structure in the mouse model to evaluate myelination defects. The study measured G-ratio (ratio of inner axonal diameter to total outer diameter) as an indicator of myelination integrity. Increased G-ratios were observed, indicating impaired myelination of axons and providing a mechanistic explanation for the visual impairment phenotype.

TARGET GENE
Gabra1, Gabrg2
MODEL SYSTEM
Gabra1+/-/Gabrg2+/- mice
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
GABAergic neurotransmission affecting myelination
SOURCE
extracted_from_pmid_37703949
PRIMARY OUTCOME
G-ratio of optic nerve axons

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%) 0.880 composite

📖 Wiki Pages

GABRG2 Protein — GABA-A Receptor Gamma2 SubunitproteinGABRA1 ProteinproteinGABRG2 — GABA-A Receptor Gamma2 SubunitgeneGABRA1 Genegene

Protocol

Protocol: Optic Nerve Myelination Analysis in Gabra1/Gabrg2 Mutant Mice

Study Design


Histological and ultrastructural analysis of optic nerve myelination in Gabra1+/-/Gabrg2+/- mice (model of epilepsy with optic atrophy) compared to WT littermates.

Animals and Tissue Preparation

  • Gabra1+/-/Gabrg2+/- mutant mice (n=8 per genotype) and WT controls (n=8)
  • At 12 weeks (adult), perfuse transcardially with 4% PFA/PBS
  • Dissect optic nerves, post-fix in 2% glutaraldehyde/2% PFA overnight at 4°C
  • Osmium tetroxide post-fixation: 1% OsO4 in 0.1M cacodylate buffer for 2 hours
  • Dehydrate through graded ethanol series (50%, 70%, 90%, 100%)
  • Embed in Epon resin for semithin (0.5 µm) and ultrathin (70 nm) sectioning

    • ...

    Expected Outcomes

    Expected Outcomes

    Primary Outcomes

  • Axon loss: 15-30% reduction in total optic nerve axon count in Gabra1/Gabrg2 mutants vs WT
  • Myelin thinning: Decreased myelin sheath thickness, elevated G-ratio (axon diameter / fiber diameter ratio approaches 1.0)
  • Demyelination: Increased percentage of unmyelinated axons in mutants
  • Ultrastructural defects: Myelin lamellar loosening, vacuolization, or axon degeneration

    • ...

    Success Criteria

    Success Criteria

    Primary

    • [ ] ≥6 animals per genotype yield analyzable histology
    • [ ] Axon count ≥ 500 per optic nerve cross-section
    • [ ] G-ratio significantly different between genotypes (p < 0.05)
    • [ ] Myelin thickness ≥10% difference between groups

    Secondary

    • [ ] Electron microscopy quality: clear myelin lamellae at 20,000x
    • [ ] Correlation between genotype and pathology severity
    • [ ] Sex included as biological variable in analysis

    ...

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