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bioRxiv · 10.1101/2025.11.25.690358

A New Approach to Modeling LGMDR1: Pyrvinium-Treated capn3b crispant Zebrafish

Ruiz-Roldan, C.·Valls, A.·Immanuel, J.·De Santis, F.·Fernandez-Torron, R.·Lopez de Munain, A.·Saenz, A.
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Abstract

The lack of an accurate animal model for LGMDR1 is a major obstacle to therapeutic development. While murine models do not replicate the human gene expression profile, zebrafish offers a promising alternative. We generated a capn3b mutant zebrafish, which showed minimal phenotypic changes. However, when this model was treated with pyrvinium, a Wnt signaling inhibitor, its gene expression patterns mimic those observed in LGMDR1 patients, reinforcing the role of the Wnt pathway in LGMDR1 pathology. This pharmacologically enhanced model, despite lacking a clear phenotype in young larvae, could serve as a valuable tool for identifying potential therapeutic targets upon further investigation and validation.

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Ruiz-Roldan, C., Valls, A., Immanuel, J., De Santis, F., Fernandez-Torron, R., Lopez de Munain, A., Saenz, A.. 2025-11-27. A New Approach to Modeling LGMDR1: Pyrvinium-Treated capn3b crispant Zebrafish. https://doi.org/10.1101/2025.11.25.690358

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