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Fibrodysplasia ossificans progressiva: mechanisms and models of skeletal metamorphosis.
Dis Model Mech. 2012 Nov; 5(6):756-62.DM

Abstract

Fibrodysplasia ossificans progressiva (FOP; MIM #135100) is a debilitating genetic disorder of connective tissue metamorphosis. It is characterized by malformation of the great (big) toes during embryonic skeletal development and by progressive heterotopic endochondral ossification (HEO) postnatally, which leads to the formation of a second skeleton of heterotopic bone. Individuals with these classic clinical features of FOP have the identical heterozygous activating mutation (c.617G>A; R206H) in the gene encoding ACVR1 (also known as ALK2), a bone morphogenetic protein (BMP) type I receptor. Disease activity caused by this ACVR1 mutation also depends on altered cell and tissue physiology that can be best understood in the context of a high-fidelity animal model. Recently, we developed such a knock-in mouse model for FOP (Acvr1(R206H/+)) that recapitulates the human disease, and provides a valuable new tool for testing and developing effective therapies. The FOP knock-in mouse and other models in Drosophila, zebrafish, chickens and mice provide an arsenal of tools for understanding BMP signaling and addressing outstanding questions of disease mechanisms that are relevant not only to FOP but also to a wide variety of disorders associated with regenerative medicine and tissue metamorphosis.

Authors+Show Affiliations

Departments of Orthopaedic Surgery, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Frederick.Kaplan@uphs.upenn.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

23115204

Citation

Kaplan, Frederick S., et al. "Fibrodysplasia Ossificans Progressiva: Mechanisms and Models of Skeletal Metamorphosis." Disease Models & Mechanisms, vol. 5, no. 6, 2012, pp. 756-62.
Kaplan FS, Chakkalakal SA, Shore EM. Fibrodysplasia ossificans progressiva: mechanisms and models of skeletal metamorphosis. Dis Model Mech. 2012;5(6):756-62.
Kaplan, F. S., Chakkalakal, S. A., & Shore, E. M. (2012). Fibrodysplasia ossificans progressiva: mechanisms and models of skeletal metamorphosis. Disease Models & Mechanisms, 5(6), 756-62. https://doi.org/10.1242/dmm.010280
Kaplan FS, Chakkalakal SA, Shore EM. Fibrodysplasia Ossificans Progressiva: Mechanisms and Models of Skeletal Metamorphosis. Dis Model Mech. 2012;5(6):756-62. PubMed PMID: 23115204.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fibrodysplasia ossificans progressiva: mechanisms and models of skeletal metamorphosis. AU - Kaplan,Frederick S, AU - Chakkalakal,Salin A, AU - Shore,Eileen M, PY - 2012/11/2/entrez PY - 2012/11/2/pubmed PY - 2013/4/23/medline SP - 756 EP - 62 JF - Disease models & mechanisms JO - Dis Model Mech VL - 5 IS - 6 N2 - Fibrodysplasia ossificans progressiva (FOP; MIM #135100) is a debilitating genetic disorder of connective tissue metamorphosis. It is characterized by malformation of the great (big) toes during embryonic skeletal development and by progressive heterotopic endochondral ossification (HEO) postnatally, which leads to the formation of a second skeleton of heterotopic bone. Individuals with these classic clinical features of FOP have the identical heterozygous activating mutation (c.617G>A; R206H) in the gene encoding ACVR1 (also known as ALK2), a bone morphogenetic protein (BMP) type I receptor. Disease activity caused by this ACVR1 mutation also depends on altered cell and tissue physiology that can be best understood in the context of a high-fidelity animal model. Recently, we developed such a knock-in mouse model for FOP (Acvr1(R206H/+)) that recapitulates the human disease, and provides a valuable new tool for testing and developing effective therapies. The FOP knock-in mouse and other models in Drosophila, zebrafish, chickens and mice provide an arsenal of tools for understanding BMP signaling and addressing outstanding questions of disease mechanisms that are relevant not only to FOP but also to a wide variety of disorders associated with regenerative medicine and tissue metamorphosis. SN - 1754-8411 UR - https://www.unboundmedicine.com/medline/citation/23115204/Fibrodysplasia_ossificans_progressiva:_mechanisms_and_models_of_skeletal_metamorphosis_ L2 - http://dmm.biologists.org/lookup/pmidlookup?view=long&pmid=23115204 DB - PRIME DP - Unbound Medicine ER -