International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)

Plenary Presentations * Oral Presentations *
Poster Presentations: Complex Genetics and Disease Modifiers * Developmental Genetics * Functional Genomics * Gene Discovery * Genetic Manipulations to Alter Gene Function * Mouse Models: Human Disease and Pharmacogenetics * Sequence Annotation and Comparative Analysis of Genomes *
Attendees * Sponsors * Table of Contents * Photographs * Awards

POSTER 96 - ELEVEN MOUSE MUTANTS WITH VESTIBULAR DEFECTS ALL MAP TO CENTROMERIC CHROMOSOME 4

K Hawker
MRC Institute of Hearing Research

1) Pau H, 1) Erven A, 1) Kiernan A, 2) Brown S, 2) Nolan P, 3) Hrabe de Angelis M, 4) Guenet J-L, 1) Steel KP
1) MRC Institute of Hearing Research, 2) MRC Mammalian Genetics Unit, 3) Institut fur Saugetiergenetik,4) Institut Pasteur

Previous work in our laboratory has characterised 7 mouse mutants from the Harwell ENU mutagenesis programme that all exhibited circling and hyperactivity, suggesting a vestibular defect. Phenotypic analysis revealed that the lateral semi-circular canal was either severely truncated or absent altogether. Backcross analysis mapped all these mutations to centromeric chromosome 4 (Kiernan et al 2002), where the Wheels mouse mutation had previously been mapped (Alavizadeh et al 2001).  The aims of this project are to identify the gene responsible for causing these defects, and investigate its role during inner ear development. We would also like to determine a reason why this region of chromosome 4 seems to be so highly mutable when exposed to ENU.Subsequently, 3 mouse mutants were recovered from the Munich ENU mutagenesis programme which also exhibited similar abnormal behaviour. Further investigation revealed similar abnormalities of the lateral semi-circular canal and backcross analysis indicated that these mouse mutations also mapped to the centromeric region of chromosome 4.  Through further backcrossing experiments, we have narrowed the mutated region down to approximately 500kb. Candidate genes within this region are currently being sequenced for mutations. Once the gene has been identified, its expression pattern during embryogenesis will be analysed to help elucidate how it is involved in development of  the ear. Additionally, identification of the gene may provide an explanation as to why this locus is so susceptible to ENU mutagenesis.