mdfw:A Deafness Susceptibility Locus That Interacts with Deaf Waddler (dfw)

• Published in: Genomics (San Diego, Calif.) Calif.), 1997-09, Vol.44 (3), p.266-272
• Main Authors: Noben-Trauth, Konrad, Zheng, Qing Yin, Johnson, Kenneth R., Nishina, Patsy M.
• Format: Article
• Language: English
• Subjects: Alleles; Animals; Biological and medical sciences; Chromosome Mapping; Classical genetics, quantitative genetics, hybrids; Deafness - genetics; Deafness - physiopathology; Disease Susceptibility; Evoked Potentials, Auditory, Brain Stem - genetics; Fundamental and applied biological sciences. Psychology; Genetic Carrier Screening; Genetic Markers; Genetics of eukaryotes. Biological and molecular evolution; Homozygote; Mice; Mice, Inbred A; Mice, Inbred AKR; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Neurologic Mutants; Microsatellite Repeats; Phenotype; Vertebrata
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1997.4869

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 withdfw.We found that CBy-dfw2J/dfw2Jhomozygotes 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 indfw2J/+ heterozygotes, was segregating in the CBy/CAST-dfw2Jintercross. By linkage analysis, we localized this locus (mdfw) to Chromosome 10, between markersD10Mit127andD10Mit185,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-derivedmdfwallele (Mdfw) retain their normal hearing function. Our results reveal an epistatic relationship between themdfwand thedfwgenes and provide a model system to study nonsyndromic hearing loss in mice.