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

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.