PUBLICATION
Functional comparison of human ACVR1 and zebrafish Acvr1l FOP-associated variants in embryonic zebrafish
- Authors
- Lalonde, R.L., Nicolas, H.A., Cutler, R.S., Pantekidis, I., Zhang, W., Yelick, P.C.
- ID
- ZDB-PUB-230107-1
- Date
- 2023
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 252(5): 605-628 (Journal)
- Registered Authors
- Yelick, Pamela C.
- Keywords
- none
- MeSH Terms
-
- Activin Receptors, Type I*/genetics
- Animals
- Embryo, Nonmammalian*/metabolism
- Humans
- Mutation
- Myositis Ossificans*
- Ossification, Heterotopic*
- Signal Transduction
- Zebrafish
- PubMed
- 36606464 Full text @ Dev. Dyn.
Citation
Lalonde, R.L., Nicolas, H.A., Cutler, R.S., Pantekidis, I., Zhang, W., Yelick, P.C. (2023) Functional comparison of human ACVR1 and zebrafish Acvr1l FOP-associated variants in embryonic zebrafish. Developmental Dynamics : an official publication of the American Association of Anatomists. 252(5):605-628.
Abstract
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, ACVR1R206H , shows increased BMP signaling and activation by Activins.
Results Here we performed in vivo functional characterization of human ACVR1R206H and orthologous zebrafish Acvr1lR203H using early embryonic zebrafish dorsoventral patterning as a phenotypic readout for receptor activity. Our results showed that human ACVR1R206H and zebrafish Acvr1lR203H exhibit functional differences in early embryonic zebrafish, and that human ACVR1R206H retained its signaling activity in the absence of a ligand-binding domain (LBD). We also showed, for the first time, that zebrafish Acvr2ba/Acvr2bb receptors are required for human ACVR1R206H signaling in early embryonic zebrafish.
Conclusions Together, these data provide new insight into ACVR1R206H signaling pathways that may facilitate the design of new and effective therapies for FOP patients. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping