International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

H3 New Mouse Models for Inherited Deafness

Alexandra Erven1, Amy E. Kiernan1, Martin Hrabé de Angelis2, Helmut Fuchs2, Rudi Balling2, Jean-Louis Guenet3, Karen B. Avraham4, Orit Ben-David4, Sarah Vreugde4, Pat Nolan5, Jo Peters5, Bruce Cattanach5, Michael Skynner6, Nick Allen6, Steve D. M. Brown5 and Karen P. Steel1. 1MRC Institute of Hearing Research, University Park, Nottingham, NG7 2RD, UK; 2GSF-Forschungszentrum für Umwelt und Gesundheit, GMBH, Institut für Säugetiergenetik, Neuherberg, Postfach 1129, Oberschleißheim, 85758, Bavaria, Germany; 3Unité de Génétique des Mammifères de l'Institute Pasteur, Rue du Docteur Roux 25, Paris, 75724/Cedex 15, France ; 4Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel; 5Mammalian Genetics Unit, MRC, Harwell, Didcot, OX11 0RD, UK; 6Department of Neurobiology, Babraham Institute, Babraham, Cambridge, CB2 4AT, UK

Mouse mutants have helped immensely in the understanding of the genetics of hearing. Positional cloning of deaf mouse mutants has shed light on a number of genes involved in causing deafness. However, a great number of human deafness loci do not have mouse models in which to analyse the phenotype. This project will attempt to address this deficiency in mouse models for deafness and vestibular mutations by the generation and analysis of new deaf mutants.

Three existing stocks have been analysed. One mutant, Hsc, arose by X-ray mutagenesis and is associated with a chromosomal translocation. This dominant mutation results in deafness, circling and head shaking behaviour, associated with thin semi-circular canals. An inbred strain, 101/H, shows progressive deafness and the middle ear ossicles are affected. A recessive mutant (Tde) presented here is due to an transgenic insertional mutation. This mutation leads to thin and disorganised stereocilia of both inner and outer hair cells of the cochlea.

A deafness screen has been added to existing ENU (N-ethyl-N-nitrosourea) mutagenesis programmes (MRC Harwell and GSF Munich). The mice are screened using a calibrated tone burst of 20kHz at 90dB SPL and monitored for a Preyer reflex (ear flick). Their behaviour is also monitored for circling or head tossing, indicative of a mutation affecting the vestibular system. The screen has resulted in 32 confirmed dominant mutants comprising 11 deaf mutants, 3 deaf and vestibular mutants and 18 vestibular mutants. Two ENU mutants are presented here (Dor and Bth); both are deaf but show two distinctly different phenotypes. One mutant has abnormal middle ear ossicles while in the other mutant the inner hair cells of the cochlea are absent.

These mutants will help considerably with the unravelling of the genetics of deafness and the understanding of the development of the mammalian inner ear.


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