ZeEfficacy

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Duchenne Muscular Dystrophy(DMD) Model

Muscle tissue specification, development and function in zebrafish is highly conserved.

 Due to its fast development, therapeutics can be studied much earlier.
Transparent and accessible embryos allow for non-invasive tissue analysis, immunohistochemistry and automated locomotion monitoring.

Zebrafish has become a fast, high-throughput assay for evaluation of therapies against Duchenne muscular dystrophy (DMD)

Method description

Wild-type zebrafish embryos

Dystrophin mutant embryos (Sapje) are exposed to the molecule of interest in order to determine dose-effect curves. 

Muscle Integrity is evaluated through optical birefringence, resulting from the diffraction of polarized light through the pseudo-crystalline array of the muscle sarcomeres.
Phenotypic analysis must be coupled with genotypic homozygous confirmation to determine true rescues.

Sapje mutant backgrounds

Muscle damage, as seen in Sapje mutant, is detected by reduction in the birefringence, showing as dark areas in the muscles.

Readouts

  • Muscle integrity: By optical birefringence.
  • Genotyping: Individual phenotype-genotype correlations in homozygous, heterozygous and wildtype (wt) larvae.
  • Immunohistochemistry (Optional): Staining against dystrophin and actin (Phalloidin-FITC) for muscle characterization.
  • Locomotion activity (Optional): Through automated video monitoring.