The Fgfr2(S252W/+) mutation in mice retards mandible formation and reduces bone mass as in human Apert syndrome.

Abstract

Apert syndrome is a common craniosynostosis caused by gain-of-function missense mutations of fibroblast growth factor receptor 2 (FGFR2). Mice with the FGFR2 S252W mutation can elucidate the mechanism by which the human Apert syndrome phenotypes arise. However, many studies have focused on mutant skull and long bone malformation, only few studies have focused on mandible changes. Bone formation and micro-architecture between 28- and 56-day-old mutant mice and controls were compared to investigate the changes in the mandibular micro-architecture caused by the Fgfr2(S252W/+) mutation to provide a basis for exploring the pathogenesis and therapeutic measures of human Apert syndrome. Fgfr2(S252W/+) mutant mice were established, and their general characteristics, including weight, naso-anal length, and calcium and phosphate content in serum and bone were tested. Calcein labeling, tartrate-resistant acid phosphatase staining and toluidine blue staining were used to detect osteoblast and osteoclast activities. H&E staining and micro-CT detection were used to test micro-architecture changes. The changes in mineral apposition rate and micro-architecture of the Fgfr2(S252W/+) mice were statistically significant; however, the magnitude of the micro-architecture became less with age. The Fgfr2(S252W/+) mutation may retard mandibular bone formation, decreased bone volume, and compromised skeletal architecture by regulating both osteoblastogenesis and osteoclastogenesis.

• Authors: Xia Zhou, Dongquan Pu, Ri Liu, Xiangjie Li, Xiujie Wen, Li Zhang, Lin Chen, Manjing Deng, Luchuan Liu
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 161A Issue 5 Pg. 983-92 (May 2013) ISSN: 1552-4833 [Electronic] United States
• PMID: 23495007 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• Phosphates
• Fgfr2 protein, mouse
• Receptor, Fibroblast Growth Factor, Type 2
• Calcium

Topics

• Acrocephalosyndactylia (genetics)
• Animals
• Bone Density (genetics)
• Bone and Bones (metabolism, pathology)
• Calcium (blood)
• Disease Models, Animal
• Humans
• Mandible (metabolism, pathology)
• Mice
• Mutation
• Osteogenesis (genetics)
• Phosphates (blood)
• Receptor, Fibroblast Growth Factor, Type 2 (genetics)