Hearing loss associated with the modifier of deaf waddler (mdfw) locus corresponds with age-related hearing loss in 12 inbred strains of mice

The modifier of deaf waddler (mdfw) and age-related hearing loss (Ahl) loci were both discovered as inbred strain polymorphisms that affect hearing lo ss in mice. Both loci map to the same position on chromosome (Chr) 10. The mdfw locus interacts epistatically with the deaf waddler (dfw) mutation on Chr 6, and the Ahl locus is a major contributor to AHL in several inbred st rains. To investigate the possibility of allelism, we examined the correspo ndence of mdfw and Ahl phenotypes among 12 inbred mouse strains. The effect s of strain-specific mdfw alleles on hearing loss were assessed in dfw(2J)/ + F1 hybrids produced from mating BALB-dfw(2J)/+ mice with mice from each o f 12 inbred strains. F1 hybrids were then assessed for hearing by auditory- evoked brainstem response threshold analysis and classified as dfw(2J)/+ or +/+ by polymerase chain reaction typing. Heterozygosity for dfw(2J) accele rated hearing Loss in F1 hybrids derived from all strains tested, except th ose produced with the B6.CAST + (Ahl) congenic strain. dfw-(2J)/+ F1 hybrid s derived from parental strains 129P1/ReJ, A/J, BUB/BnJ, C57BR/cdJ, DBA/2J, NOD/LtJ and SKH2/J exhibited a severe hearing loss by 12 weeks of age. Tho se derived from strains 129T2/SvEmsJ, C3H/HeJ, CBA/CaJ and NON/LtJ exhibite d only a slight to intermediate hearing loss at that age. The hearing loss associated with these strain-specific mdfw alleles corresponds with previou sly determined Ahl allele effects, providing additional evidence that mdfw and Ahl are manifestations of the same gene. A functional relationship ther efore may exist between the Ca2+ transporting activity of the dfw gene (Atp 2h2) and AHL. (C) 2001 published by Elsevier Science B.V.