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

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 (dfw(2J)) and present evidence for a hearing susceptibility locus (mdfw) that interacts with dfw. We found that CBy-dfw(2J)/dfw(2J) homozygotes exhibit no discernible auditory brainstem responses (ABR) to sound pressure level stimuli up to 100 dB, indicating a profound deafness. Interestingly, the ABR iu CBy-dfw(2J)/+ 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-dfw(2J)/+ heterozygotes displayed increased ABR thresholds, suggesting that a second locus, controlling heaping function in dfw(2J)/+ heterozygotes, was segregating in the CBy/CAST-dfw(2J) 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-dfw(2J)/+ heterozygotes that develop hearing loss are homozygous for the CBy-derived recessive allele (mdfw(c)). In contrast, CBy/CAST-dfw(2J)/+ heterozygotes expressing even a single copy of the CAST/Ei-derived mdfw allele (Mdfw) retain their normal heaping 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. (C) 1997 Academic Press.