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Dock3 is essential for normal myogenic fusion and alters dystrophin-deficiency pathologies

ABSTRACT: DOCK3 is a member of the DOCK family of guanine nucleotide exchange factors that function to regulate cell migration, fusion, and overall viability. Previously, we identified a miR-486/Dock3 signaling cascade that was dysregulated in dystrophin-deficient muscle which resulted in the overexpression of DOCK3, however not much else is known about the role of DOCK3 in muscle. In this work, we characterize the functional role of DOCK3 in normal and dystrophic striated muscle. By utilizing the Dock3 global knockout (Dock3 KO) mice, we found reducing Dock3 gene via haploinsufficiency in DMD mice improved muscle histology, however full loss of Dock3 worsened overall muscle function on a dystrophin-deficient background. Consistent with this, Dock3 KO mice have impaired muscle architecture, myoblast fusion defects, and cardiac functional deficits. Moreover, transcriptomic analyses of Dock3 knockout muscles reveal a decrease in factors known for myoblast fusion, suggesting a possible mechanism of action. These studies identify DOCK3 as a novel modulator of muscle fusion and muscle health, and may yield additional therapeutic targets for treating dystrophic muscle symptoms.

ORGANISM(S): Mus musculus

PROVIDER: GSE141621 | GEO | 2020/12/24

REPOSITORIES: GEO

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