Characterization of a New Mouse Mutant, Flouncer, with a... : Otology & Neurotology (original) (raw)

Genetics of Hearing Loss

Characterization of a New Mouse Mutant, Flouncer, with a Balance Defect and Inner Ear Malformation

Pau, Henry*; Hawker, Kelvin*; Fuchs, Helmut†; De Angelis, Martin Hrabé†; Steel, Karen P.*‡

*MRC Institute of Hearing Research, University Park, Nottingham, U.K., †GSF Research Center for Environment and Health, Institute of Experimental Genetics, Neuherberg, Germany, and ‡Wellcome Trust Sanger Institute, Hinxton, Cambridge, U.K.

This work was supported by the MRC (K. P. S.), Defeating Deafness (K. P. S.), the EC (CT97-2715 and QLG2-CT-1999-00988; K. P. S. and M. H. D. A.), the German Human Genome Project, the German National Genome Network, a CRS Amplifon Fellowship (H. P.), and an MRC/RCSEd Clinical Research Training Fellowship (H. P.)

Address correspondence and reprint requests to Karen P. Steel, Ph.D., F.Med.Sci., Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, U.K.; Email: [email protected]

Abstract

Hypothesis:

Balance anomalies are often associated with abnormalities of the vestibular part of the inner ear. We studied a newly generated mouse mutant with balance defects and asked whether its behavioral anomalies were associated with inner ear defects. Furthermore, we asked whether the mutation responsible for the defects was located in the same region of mouse chromosome 4 as several other mouse mutations that we have previously described.

Background:

Phenotypic and genotypic analysis of mouse mutants with hearing or balance problems has helped greatly with the identification of the genes involved in deafness and has contributed to the understanding of mechanisms of normal hearing and balance. This article describes a new mouse mutant, flouncer, that shows a balance defect. The flouncer mutation shows semidominant inheritance, and was generated by mutagenesis using N- ethyl-N- nitrosourea.

Methods:

Hearing was assessed by the Preyer reflex (ear-flick) test. Behavioral tests including open field and swimming tests were performed. The morphology of the middle and inner ears was investigated by microdissection, clearing using glycerol, paint-filling of the labyrinth, and scanning electron microscopy.

Results:

Flouncer mutants showed vestibular dysfunction but do respond to sounds. Phenotypically, mutants had various degrees of truncation of the lateral semicircular canals, small or obliterated round window of the cochlea, and mild morphologic anomalies of the stapes. Flouncer mutants showed circling behavior and hyperactivity. Linkage mapping using a backcross has indicated that the mutation lies in proximal chromosome 4 proximal to D4Mit171.

Conclusion:

The lateral semicircular canal has been described to be the most commonly affected part of the inner ear in humans, and flouncer provides a mouse model for genetic and developmental analysis of such defects.