IDENTIFICATION AND LOCALIZATION OF TYPE-IV COLLAGEN CHAINS IN THE INNER-EAR COCHLEA

Mutations in the genes encoding the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains of type IV collagen have been implicated in the pathogen esis of Alport's syndrome, a hereditary disorder characterized by prog ressive nephropathy and sensorineural deafness. The known expression o f these chains in kidney basement membranes supports the contention th at they play a crucial role in the ultrafiltration function. Whether t hey play a role in auditory signal transduction remains unknown as her etofore, they have not been identified in the inner ear. In the presen t study, the expression of type IV collagen in cochlea of the inner ea r of guinea pigs was determined. All six alpha-chains of type IV colla gen were identified by biochemical and immunological methods. By indir ect immunofluorescence, alpha 1(IV) and alpha 2(IV) chains were locali zed to the spiral limbus, basilar membrane and tectorial membrane, The alpha 3(IV), alpha 4(IV), alpha 5(IV) and alpha 6(IV) chains localize d exclusively to the tectorial membrane and basilar membrane. These re sults suggest a possible role of type IV collagen chains in the active tuning of the basilar and tectorial membrane, an essential step in fr equency discrimination and amplification of auditory signals.