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 (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.
Noben-Trauth
K
K
Jackson Laboratory, Bar Harbor, Maine 04609, USA. kntrauth@pop.nidcd.nih.gov
Zheng
Q Y
QY
Johnson
K R
KR
Nishina
P M
PM
D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D003638:Deafness / Q000235:genetics* / Q000503:physiopathology; D004198:Disease Susceptibility; D016057:Evoked Potentials, Auditory, Brain Stem / Q000235:genetics; D006580:Genetic Carrier Screening; D005819:Genetic Markers; D006720:Homozygote; D051379:Mice; D008805:Mice, Inbred A; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008818:Mice, Neurologic Mutants; D018895:Microsatellite Repeats; D010641:Phenotype
D005819:Genetic Markers