Functional comparison of human ACVR1 and zebrafish Acvr1l FOP-associated variants in embryonic zebrafish.

Background: Fibrodysplasia ossificans progressiva (FOP), a rare disease characterized by progressive heterotopic ossification of muscle and connective tissues, is caused by autosomal dominant activating mutations in the type I receptor, ACVR1/ALK2. The classic human FOP variant, ACVR1 , shows increased bone morphogenetic protein (BMP) signaling and activation by activins.

Results: Here, we performed in vivo functional characterization of human ACVR1 and orthologous zebrafish Acvr1l using early embryonic zebrafish dorsoventral patterning as a phenotypic readout for receptor activity.