Deafness in Claudin 11-null mice reveals the critical contribution of basal cell tight junctions to stria vascularis function.
Generation of a strong electrical potential in the cochlea is uniquely mammalian and may reflect recent evolutionary advances in cellular voltage-dependent amplifiers. This endocochlear potential is hypothesized to dramatically improve hearing sensitivity, a concept that is difficult to explore experimentally, because manipulating cochlear function frequently causes rapid degenerative changes early in development. Here, we examine the deafness phenotype in adult Claudin 11-null mice, which lack the basal cell tight junctions that give rise to the intrastrial compartment and find little evidence of cochlear pathology. Potassium ion recycling is normal in these mutants, but endocochlear potentials were below 30 mV and hearing thresholds were elevated 50 dB sound pressure level across the frequency spectrum. Together, these data demonstrate the central importance of basal cell tight junctions in the stria vascularis and directly verify the two-cell hypothesis for generation of endocochlear potential. Furthermore, these data indicate that endocochlear potential is an essential component of the power source for the mammalian cochlear amplifier.
Gow
Alexander
A
Center for Molecular Medicine and Genetics, Carman and Ann Adams Department of Pediatrics, Wayne State University, Detroit, Michigan 48201, USA. agow@genetics.wayne.edu
Davies
Caroline
C
Southwood
Cherie M
CM
Frolenkov
Gregory
G
Chrustowski
Mark
M
Ng
Lily
L
Yamauchi
Daisuke
D
Marcus
Daniel C
DC
Kachar
Bechara
B
D000818:Animals; D002470:Cell Survival; D062445:Claudin-1; D057167:Claudins; D003638:Deafness / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D004058:Diffusion; D004594:Electrophysiology; D004710:Endolymph / Q000378:metabolism; D042783:Endothelial Cells / Q000648:ultrastructure; D005074:Evoked Potentials, Visual; D006198:Hair Cells, Auditory / Q000473:pathology; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D017084:Otoacoustic Emissions, Spontaneous; D011188:Potassium / Q000378:metabolism; D021381:Protein Transport; D013136:Spiral Ganglion / Q000473:pathology; D013316:Stria Vascularis / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D019108:Tight Junctions / Q000378:metabolism / Q000648:ultrastructure*
D062445:Claudin-1; D057167:Claudins; C568113:Cldn1 protein, mouse; C492354:Cldn11 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011188:Potassium