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Steven E. Sobol, MD, MSc; Xiuyin Teng, MSc; E. Bryan Crenshaw III, PhD

Arch Otolaryngol Head Neck Surg. 2005;131:41-45.

Objective  To examine the developmental time course of the mutant phenotype and cellular mechanisms that result in malformations of the superior semicircular canal (SSCC) in Brn4 knockout mice. Mutations in the Brn4/Pou3f4 gene result in characteristic inner ear abnormalities in mutant mouse pedigrees, and the findings in these mice are similar to those in human X-linked deafness type III.

Design  Mutant and control mice were killed at various neonatal time points to assess the development of the SSCC. Measurements of SSCC diameter were made on paint-perfused specimens at postnatal day (P) 0, P7, P10, and P14. Histologic evaluation of the SSCC was made on hematoxylin-eosin–stained sections at P10.

Results  A dysmorphic constriction of the superior arc of the SSCC in Brn4 knockout mice was initially detectable at P14. Interestingly, the mutant SSCC is indistinguishable from control mice at earlier neonatal time points. In mutant neonates, there is persistence of immature woven bone with high cellularity surrounding the perilymphatic space of the SSCC. These findings are not present in control animal specimens, which demonstrate appropriate lamellar bony architecture.

Conclusions  In Brn4 knockout mice, constriction of the SSCC with narrowing of the bony labyrinth develops in the postnatal period at approximately P14. The persistence of immature bone in affected mice indicates that signaling abnormalities disrupt normal mesenchymal differentiation in the SSCC.

Author Affiliations: Division of Pediatric Otolaryngology and Mammalian Neurogenetics Group, The Center for Childhood Communication, The Children’s Hospital of Philadelphia (Drs Sobol and Crenshaw and Ms Teng); and Department of Otorhinolaryngology–Head and Neck Surgery, University of Pennsylvania School of Medicine (Drs Sobol and Crenshaw), Philadelphia. Dr Sobol is currently with the Department of Otolaryngology–Head and Neck Surgery, Emory University School of Medicine, Atlanta, Ga.

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