Mice lacking the B1 subunit of H+ -ATPase have normal hearing.
Acid-base homeostasis of endolymph is thought to be essential for normal inner ear function. This assumption was supported by clinical data from individuals affected by autosomal recessive distal renal tubular acidosis with sensorineural hearing loss. This recessive syndrome was recently demonstrated to be due to mutations in the gene encoding the B1 subunit of H(+)-ATPase (ATP6B1). To examine the potential roles of H(+)-ATPase B1 subunit in inner ear development and function, we defined its spatial and temporal expression patterns in the developing mouse inner ear and examined the morphologic and physiologic effects of loss of its function. Standard in situ hybridization was used for the expression study with routine morphologic and physiologic assessments of hearing and balance in H(+)-ATPase B1 subunit (Atp6b1) null mutant mice. Atp6b1 mRNA was first detected at embryonic day 11.5 (E11.5) in the endolymphatic duct epithelia. From E16.5 onward, Atp6b1 was also observed in the presumptive interdental cell layer of the spiral limbus in the cochlea. Auditory brainstem response tests revealed normal hearing in mice lacking Atp6b1. The inner ears of these mice develop normally and show no overt morphological abnormalities. Our data demonstrate that Atp6b1 is not critical for normal inner ear development or normal inner ear function in mice and suggest that other proton-transporting mechanisms or pH buffering systems must allow the mouse inner ear to compensate for lack of normal Atp6b1 activity.
Dou
Hongwei
H
Center for Hearing and Deafness Research, Department of Pediatric Otolaryngology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
Finberg
Karin
K
Cardell
Emma Lou
EL
Lifton
Richard
R
Choo
Daniel
D
D000161:Acoustic Stimulation; D000818:Animals; D000831:Animals, Newborn; D001309:Auditory Threshold; D003051:Cochlea / Q000196:embryology; D007758:Ear, Inner / Q000473:pathology; D004622:Embryo, Mammalian / Q000378:metabolism; D005314:Embryonic and Fetal Development; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D006309:Hearing / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D021122:Protein Subunits / Q000235:genetics / Q000502:physiology*; D014018:Tissue Distribution; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000502:physiology*
D021122:Protein Subunits; D025262:Vacuolar Proton-Translocating ATPases