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Child's Nervous System
Published in: Child's Nervous System 9/2012

01-09-2012 | Special Annual Issue

Phenotype profile of a genetic mouse model for Muenke syndrome

Authors: Hyun-Duck Nah, Eiki Koyama, Nneamaka B. Agochukwu, Scott P. Bartlett, Maximilian Muenke

Published in: Child's Nervous System | Issue 9/2012

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Abstract

Purpose

The Muenke syndrome mutation (FGFR3 P250R ), which was discovered 15 years ago, represents the single most common craniosynostosis mutation. Muenke syndrome is characterized by coronal suture synostosis, midface hypoplasia, subtle limb anomalies, and hearing loss. However, the spectrum of clinical presentation continues to expand. To better understand the pathophysiology of the Muenke syndrome, we present collective findings from several recent studies that have characterized a genetically equivalent mouse model for Muenke syndrome (FgfR3 P244R ) and compare them with human phenotypes.

Conclusions

FgfR3 P244R mutant mice show premature fusion of facial sutures, premaxillary and/or zygomatic sutures, but rarely the coronal suture. The mice also lack the typical limb phenotype. On the other hand, the mutant mice display maxillary retrusion in association with a shortening of the anterior cranial base and a premature closure of intersphenoidal and spheno-occipital synchondroses, resembling human midface hypoplasia. In addition, sensorineural hearing loss is detected in all FgfR3 P244R mutant mice as in the majority of Muenke syndrome patients. It is caused by a defect in the mechanism of cell fate determination in the organ of Corti. The mice also express phenotypes that have not been previously described in humans, such as reduced cortical bone thickness, hypoplastic trabecular bone, and defective temporomandibular joint structure. Therefore, the FgfR3 P244R mouse provides an excellent opportunity to study disease mechanisms of some classical phenotypes of Muenke syndrome and to test novel therapeutic strategies. The mouse model can also be further explored to discover previously unreported yet potentially significant phenotypes of Muenke syndrome.
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Metadata
Title
Phenotype profile of a genetic mouse model for Muenke syndrome
Authors
Hyun-Duck Nah
Eiki Koyama
Nneamaka B. Agochukwu
Scott P. Bartlett
Maximilian Muenke
Publication date
01-09-2012
Publisher
Springer-Verlag
Published in
Child's Nervous System / Issue 9/2012
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-012-1778-9

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