Transgenic mice overexpressing BMP4 develop a fibrodysplasia ossificans progressiva (FOP)-like phenotype

Lixin Kan, Min Hu, William A. Gomes, John A. Kessler

Research output: Contribution to journalArticle

116 Scopus citations

Abstract

Fibrodysplasia ossificans progressiva (FOP) is a rare hereditary connective tissue disease characterized by progressive postnatal heterotopic bone formation. Although the genetic defects of FOP are not known, several lines of evidence have suggested that bone morphogenetic protein-4 (BMDP4) may be involved in the pathophysiology. Nevertheless BMP4-transgenic mice have previously failed to develop the disorder and there has been no good animal model of the disease. Here, we report that a unique transgenic mouse line that overexpresses BMP4 under control of the neuron-specific enolase (NSE) promoter develops a FOP-like phenotype. Mating of these animals with transgenic animals that overexpress the BMP inhibitor noggin prevents the disorder, confirming the role of BMP4 in the pathogenesis of the disease. Heterotopic bone formation in these animals appears to follow the classic endochondral ossification pathway. Sex-mismatched cell transplantation experiments indicate that multiple cell sources contribute to the heterotopic ossification. This remarkable animal model provides a unique opportunity to further study the role of the BMP signaling pathway in heterotopic ossification and to improve our understanding of the clinical aspects of FOP.

Original languageEnglish (US)
Pages (from-to)1107-1115
Number of pages9
JournalAmerican Journal of Pathology
Volume165
Issue number4
DOIs
StatePublished - Oct 2004

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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