Neuroepithelial defects of the inner ear in a new allele of the mouse mutation Ames waltzer

This report presents new findings regarding a recessive insertional mutatio n in the transgenic line TgN2742Rpw that causes deafness and circling behav ior in mice homozygous for the mutation. The mutant locus was mapped to a r egion on mouse chromosome 10 close to three spontaneous recessive mutations causing deafness: Ames waltzer (av), Waltzer (v), and Jackson circler (jc) Complementation testing revealed that the TgN2742Rpw mutation is allelic w ith av. Histological and auditory brainstem response (ABR) evaluation of an imals that have the new allele balanced with the av(J) allele (called compo und heterozygotes, TgN2742Rpw/av(J)) supports our genetic analysis. ABR eva luation shows complete absence of auditory response throughout the life spa n of TgN2742Rpw/av(J) compound heterozygotes. Scanning electron microscopy revealed abnormalities of inner and outer hair cell stereocilia in the coch leae of TgN2742Rpw mutants at 10 days after bi;th (DAB). The organ of Corti subsequently undergoes degeneration, leading to nearly complete loss of th e cochlear neuroepithelium in older mutants by about 50 DAB. The vestibular neuroepithelia remain morphologically normal until at least 30 DAB. Howeve r, by 50 days, degenerative changes are evident in the saccular macula, whi ch progresses to total loss of the saccular neuroepithelium in older animal s. The new allele of av reported here will be designated av(TgN2742Rpw). (C ) 2000 Elsevier Science B.V. All rights reserved.