Faculty Research 1990 - 1999

Title

mdfw: a deafness susceptibility locus that interacts with deaf waddler (dfw).

Document Type

Article

Publication Date

1997

Keywords

Animal, Chromosome-Mapping, Deafness: ge, pp, pa, Disease-Susceptibility, Evoked-Potentials-Auditory-Brain-Stem: ge, Genetic-Markers, Heterozygote-Detection, Homozygote, Mice, Mice-Inbred-A, Mice-Inbred-AKR, Mice-Inbred-BALB-C, Mice-Inbred-C57BL, Mice-Inbred-DBA, Mice-Neurologic-Mutants, Microsatellite-Repeats, Phenotype, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S

JAX Source

Genomics 1997 Sep 15;44(3):266-72

Grant

CA34196/CA/NCI, N01-DC-6-2108/DC/NIDCD

Abstract

The deaf waddler (dfw) mutation is a model system to study the biology of neuroepithelial hearing defects in mice. Here we describe the identification and characterization of a new allele of deaf waddler (dfw2J) and present evidence for a hearing susceptibility locus (mdfw) that interacts with dfw. We found that CBy-dfw2J/dfw2J homozygotes exhibit no discernible auditory brainstem responses (ABR) to sound pressure level stimuli up to 100 dB, indicating a profound deafness. Interestingly, the ABR in CBy-dfw2J/+ heterozygotes is also abnormal, showing age-dependent elevated thresholds characteristic of a progressive hearing loss. When outcrossed onto the CAST/Ei strain, only 24% of the F2 CBy/CAST-dfw2J/ + heterozygotes displayed increased ABR thresholds, suggesting that a second locus, controlling hearing function in dfw2J/+ heterozygotes, was segregating in the CBy/CAST-dfw2J intercross. By linkage analysis, we localized this locus (mdfw) to Chromosome 10, between markers D10Mit127 and D10Mit185, within a 4.0 +/- 1.1 cM genetic interval. All CBy/CAST-dfw2J/+ heterozygotes that develop hearing loss are homozygous for the CBy-derived recessive allele (mdfwC). In contrast, CBy/ CAST-dfw2J/+ heterozygotes expressing even a single copy of the CAST/Ei-derived mdfw allele (Mdfw) retain their normal hearing function. Our results reveal an epistatic relationship between the mdfw and the dfw genes and provide a model system to study nonsyndromic hearing loss in mice.

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