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 iden tification and characterization of a new allele of deaf waddler (dfw(2 J)) and present evidence for a hearing susceptibility locus (mdfw) tha t interacts with dfw. We found that CBy-dfw(2J)/dfw(2J) homozygotes ex hibit no discernible auditory brainstem responses (ABR) to sound press ure level stimuli up to 100 dB, indicating a profound deafness. Intere stingly, the ABR iu CBy-dfw(2J)/+ heterozygotes is also abnormal, show ing 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 threshold s, suggesting that a second locus, controlling heaping function in dfw (2J)/+ heterozygotes, was segregating in the CBy/CAST-dfw(2J) intercro ss. 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 he aring loss are homozygous for the CBy-derived recessive allele (mdfw(c )). In contrast, CBy/CAST-dfw(2J)/+ heterozygotes expressing even a si ngle copy of the CAST/Ei-derived mdfw allele (Mdfw) retain their norma l heaping function. Our results reveal an epistatic relationship betwe en the mdfw and the dfw genes and provide a model system to study nons yndromic hearing loss in mice. (C) 1997 Academic Press.