Strial dysfunction in the MRL-Fas(lpr) mouse

The MRL-Fas(lpr) mouse, a model of multisystemic autoimmune disease, has be en proposed as a potential model of autoimmune inner ear disease. Cochlear pathology, consisting of hydropic degeneration of the stria vascularis, has been documented to occur coincident with the establishment of systemic dis ease in this animal. Because the cochlear pathology is restricted to the st ria, this study was designed to evaluate whether the endocochlear potential (EP) would be diminished in these animals because of a loss in strial Na,K -ATPase. Experimental (MRL-Fas(lpr)) mice, with established systemic diseas e, had auditory brain stem response thresholds and EPs recorded. MRL-+/+ mi ce served as controls. Animals were then euthanized, and their cochleas wer e processed for immunohistologic assay for the alpha 1 and beta 2 subunits of Na,K-ATPase. Density of staining was evaluated by use of quantitative me ans with densitometry image analysis of digitized images. MRL-Fas(lpr) mice revealed significant elevations in auditory brain stem response thresholds and reductions in EPs but no reductions in Na,K-ATPase levels, as evidence d by immunohistochemical assay. The reduction of EP likely occurs as a resu lt of cellular degeneration within the stria vascularis and likely results from an abrogation of the strial perilymph/endolymph barrier and not from a reduction in strial Na,K-ATPase levels.