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

F16 Functional, structural and genetic analyses of waltzer (v) and mdfw

Elizabeth Bryda1, Konrad Noben-Trauth2, Hung J. Kim, Ralph H. Holme* and Karen P. Steel*. 1Dept. of Microbiology, Immunology & Molecular Genetics, Marshall University School of Medicine, Huntington, WV 25704; 2Section on Murine Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland 20850; 3MRC Institute of Hearing Research, University Park, Nottingham NG7 2RD, UK

Recessive mutations in the waltzer (v) locus cause head tossing, aberrant circling behavior and a complete auditory dysfunction in 3-4 week old mutants. On the anatomical level the auditory phenotype coincides with an early onset degeneration of the organ of Corti, which is followed by the degeneration of the spiral ganglion and the stria vascularis1. To extend the initial phenotypic analyses we performed auditory evoked brain stem response analyses (ABR) and scanning electronmicroscopy (SEM) using the C57BL/6J-v2J strain. By ABR analyses we found that 3 week old v2J homozygotes fail to produce characteristic waveforms even at a sound pressure level (SPL) of 99dB, whereas v2J/+ control littermates returned normal waveforms and thresholds (20dBSPL; n=4). SEM analysis of E18.5 v2J homozygotes showed a delay in the elongation of outer hair cell microvilli to form stereocilia. By P4, outer and inner hair cell stereocilia were disorganized and arranged in erratic clumps rather than in the normal "v"-shape pattern as observed in heterozygotes. In addition, the kinocilium was often misplaced from its lateral position to a more central or modiolar position.

We recently identified and mapped a modifier of the deaf waddler locus (named mdfw) to chromosome 102. The BALB/cByJ derived recessive mdfw allele confers progressive hearing loss to dfw2J/+ heterozygotes. Neither mdfw homozygotes nor dfw2J/+ heterozygotes per se develop hearing loss suggesting a synergistic interaction. Upon fine mapping we noticed that the mdfw critical region overlaps with the valb map location defined by the recombinant flanking markers D10Mit60 and D10Mit1723. Here we present a combined high-resolution integrated genetic, radiation hybrid and physical YAC/BAC based map of the v and mdfw critical interval. Our data suggest that both loci are allelic.

1Deol, M.S. Proc. Roy. Soc. 145, 206-213 (1955).
2Noben-Trauth, K., Zheng, Q.Y., Johnson, K.R. & Nishina, P.M. Genomics 44, 266-72 (1997).
3 Bryda, E.C., Ling, H. & Flaherty, L. Mamm Genome 8, 1-4 (1997).


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