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Strial dysfunction in the MRL-Fas mouse
M J Ruckenstein1, M Milburn, L Hu
1Department of Otolaryngology-Head and Neck Surgery, University of Tennessee, Memphis, USA.
Abstract:
The MRL-Fas(lpr) mouse, a model of multisystemic autoimmune disease, has been 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 disease in this animal. Because the cochlear pathology is restricted to the stria, 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 disease, had auditory brain stem response thresholds and EPs recorded. MRL-+/+ mice served as controls. Animals were then euthanized, and their cochleas were processed for immunohistologic assay for the alpha1 and beta2 subunits of Na,K-ATPase. Density of staining was evaluated by use of quantitative means 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 evidenced by immunohistochemical assay. The reduction of EP likely occurs as a result 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.
Insights
The MRL-Fas(lpr) mouse model shows hearing loss due to reduced endocochlear potential (EP). This decline in EP is linked to stria vascularis degeneration, not a loss of Na, K-ATPase in autoimmune inner ear disease.
Area of Science:
- Otolaryngology
- Immunology
- Genetics
Background:
- The MRL-Fas(lpr) mouse model exhibits multisystemic autoimmune disease.
- This model has been investigated for autoimmune inner ear disease, showing cochlear pathology like stria vascularis degeneration.
- The stria vascularis is crucial for maintaining the endocochlear potential (EP).
Purpose of the Study:
- To investigate the cause of diminished endocochlear potential (EP) in MRL-Fas(lpr) mice with autoimmune inner ear disease.
- To determine if reduced EP is due to a loss of strial Na, K-ATPase activity.
- To correlate auditory brain stem response (ABR) thresholds with EP and Na, K-ATPase levels.
Main Methods:
- Auditory brain stem response (ABR) thresholds and endocochlear potentials (EPs) were recorded in MRL-Fas(lpr) mice and control MRL-+/+ mice.
- Cochleas were analyzed using immunohistochemistry to quantify Na, K-ATPase alpha1 and beta2 subunit levels.
- Quantitative densitometry was used to evaluate the density of Na, K-ATPase staining.
Main Results:
- MRL-Fas(lpr) mice demonstrated significantly elevated ABR thresholds and reduced EPs compared to controls.
- Immunohistochemical analysis revealed no significant reduction in Na, K-ATPase levels in the stria vascularis of MRL-Fas(lpr) mice.
- Despite reduced EP, Na, K-ATPase expression remained intact.
Conclusions:
- The reduction in EP in MRL-Fas(lpr) mice is likely caused by cellular degeneration within the stria vascularis.
- The findings suggest that the breakdown of the strial perilymph/endolymph barrier, rather than diminished Na, K-ATPase, underlies the EP reduction.
- This study highlights the importance of strial integrity for hearing function in autoimmune inner ear disease models.