title: Slc4a11 gene disruption in mice: cellular targets of sensorineuronal abnormalities.
abstract: NaBC1 (the SLC4A11 gene) belongs to the SLC4 family of sodium-coupled bicarbonate (carbonate) transporter proteins and functions as an electrogenic sodium borate cotransporter. Mutations in SLC4A11 cause either corneal abnormalities (corneal hereditary dystrophy type 2) or a combined auditory and visual impairment (Harboyan syndrome). The role of NaBC1 in sensory systems is poorly understood, given the difficulty of studying patients with NaBC1 mutations. We report our findings in Slc4a11(-/-) mice generated to investigate the role of NaBC1 in sensorineural systems. In wild-type mice, specific NaBC1 immunoreactivity was detected in fibrocytes of the spiral ligament, from the basal to the apical portion of the cochlea. NaBC1 immunoreactivity was present in the vestibular labyrinth, in stromal cells underneath the non-immunoreactive sensory epithelia of the macula utricle, sacule, and crista ampullaris, and the membranous vestibular labyrinth was collapsed. Both auditory brain response and vestibular evoked potential waveforms were significantly abnormal in Slc4a11(-/-) mice. In the cornea, NaBC1 was highly expressed in the endothelial cell layer with less staining in epithelial cells. However, unlike humans, the corneal phenotype was mild with a normal slit lamp evaluation. Corneal endothelial cells were morphologically normal; however, both the absolute height of the corneal basal epithelial cells and the relative basal epithelial cell/total corneal thickness were significantly increased in Slc4a11(-/-) mice. Our results demonstrate for the first time the importance of NaBC1 in the audio-vestibular system and provide support for the hypothesis that SLC4A11 should be considered a potential candidate gene in patients with isolated sensorineural vestibular hearing abnormalities.
authors: Division of Head and Neck, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
authors: Ivan A
authors: IA
authors: Lopez
authors: Mark I
authors: MI
authors: Rosenblatt
authors: Charles
authors: C
authors: Kim
authors: Gary C
authors: GC
authors: Galbraith
authors: Sherri M
authors: SM
authors: Jones
authors: Liyo
authors: L
authors: Kao
authors: Debra
authors: D
authors: Newman
authors: Weixin
authors: W
authors: Liu
authors: Stacey
authors: S
authors: Yeh
authors: Alexander
authors: A
authors: Pushkin
authors: Natalia
authors: N
authors: Abuladze
authors: Ira
authors: I
authors: Kurtz
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics* / Q000378:metabolism; D017920:Antiporters / Q000235:genetics* / Q000378:metabolism; D001300:Audiometry, Evoked Response / Q000379:methods; D003051:Cochlea / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D027981:Symporters / Q000235:genetics* / Q000378:metabolism
chemical_list: D027321:Anion Transport Proteins; D017920:Antiporters; C544607:Slc4a11 protein, mouse; D027981:Symporters