Differential Expression of Genes within the Cochlea as Defined by a Custom Mouse Inner Ear Microarray

Morris, Ken A.; Snir, Einat; Pompéia, Celine; Koroleva, Irina V.; Kachar, Bechara; Hayashizaki, Yoshihide; Carninci, Piero; Soares, Marcelo B.; Beisel, Kirk W.

doi:10.1007/s10162-004-5046-x

Cited by 37 publications

(28 citation statements)

References 79 publications

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“…Three separate microarray experiments were performed: two experiments using two rounds of RNA amplification to compare expression differences between the cochleae from Slo ϩ/ϩ and Slo Ϫ/Ϫ mice and one experiment using a single round of RNA amplification to compare expression differences between the cochleae and cerebellum from Slo ϩ/ϩ mice and the cochleae from Slo Ϫ/Ϫ mice. Table 1 shows that in our experiments, transcripts known to be enriched in the cochlea (47)(48)(49)(50) are detected as 2-fold or more enriched in the cochlea in comparison with the cerebellum (both from Slo ϩ/ϩ mice). These data indicate that microarray analyses can indeed detect expression differences in the cochlea.…”

Section: Regulation Of Other Gene Products Does Not Compensate For Thmentioning

confidence: 62%

Cochlear Function in Mice Lacking the BK Channel α, β1, or β4 Subunits

Pyott

Meredith

Fodor

et al. 2007

Journal of Biological Chemistry

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Large conductance voltage-and calcium-activated potassium (BK) channels are important for regulating many essential cellular functions, from neuronal action potential shape and firing rate to smooth muscle contractility. In amphibians, reptiles, and birds, BK channels mediate the intrinsic frequency tuning of the cochlear hair cell by an electrical resonance mechanism. In contrast, inner hair cells of the mammalian cochlea are extrinsically tuned by accessory structures of the cochlea. Nevertheless, BK channels are present in inner hair cells and encode a fast activating outward current. To understand the role of the BK channel ␣ and ␤ subunits in mammalian inner hair cells, we analyzed the morphology, physiology, and function of these cells from mice lacking the BK channel ␣ (Slo ؊/؊ ) and also the ␤1 and ␤4 subunits (␤1/4 ؊/؊ ). ␤1/4 ؊/؊ mice showed normal subcellular localization, developmental acquisition, and expression of BK channels. ␤1/4 ؊/؊ mice showed normal cochlear function as indicated by normal auditory brainstem responses and distortion product otoacoustic emissions. Slo ؊/؊ mice also showed normal cochlear function despite the absence of the BK␣ subunit and the absence of fast activating outward current from the inner hair cells. Moreover, microarray analyses revealed no compensatory changes in transcripts encoding ion channels or transporters in the cochlea from Slo ؊/؊ mice. Slo ؊/؊ mice did, however, show increased resistance to noise-induced hearing loss. These findings reveal the fundamentally different contribution of BK channels to nonmammalian and mammalian hearing and suggest that BK channels should be considered a target in the prevention of noise-induced hearing loss.

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Section: Regulation Of Other Gene Products Does Not Compensate For Thmentioning

confidence: 62%

Cochlear Function in Mice Lacking the BK Channel α, β1, or β4 Subunits

Pyott

Meredith

Fodor

et al. 2007

Journal of Biological Chemistry

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“…This is the first study demonstrating the expression of NaBC1 protein in the mammalian cochlea. In an earlier study using a mouse inner ear microarray, Slc4a11 message was detected in the lateral wall of the cochlea (24). This finding was interpreted as having localized the cotransporter to the stria vascularis (14).…”

Section: Discussionmentioning

confidence: 88%

Slc4a11 Gene Disruption in Mice

López

Rosenblatt

Kim

et al. 2009

Journal of Biological Chemistry

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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.The SLC4 transporter family consists of proteins that mediate bicarbonate (carbonate) transport and include Cl-HCO 3 exchangers, Na/HCO 3 cotransporters, and sodium-driven Cl-HCO 3 exchangers (1). A single member of the family encoded by the SLC4A11 gene does not transport bicarbonate (carbonate) (2, 3). On the basis of sequence homology with other members of the SLC4 family, the protein encoded by SLC4A11 was initially called BTR1 (bicarbonate transporter 1) (2). Subsequently, motivated by its homology with the borate transporter BOR1 in Arabidopsis (4), experiments by Park et al. (3) reported that the transporter functioned in the presence of borate as an electrogenic sodium-borate cotransporter and was renamed NaBC1.Mutations in the SLC4A11 gene are responsible for corneal hereditary dystrophy type 2 (CHED2) 4 and Harboyan syndrome (5-14). In addition to corneal dystrophy, patients with Harboyan syndrome have perceptive hearing loss and nystagmus (7,14). Whether all patients with CHED2 have undiagnosed hearing abnormalities is currently unknown. Heterozygous single nucleotide polymorphisms for SLC4A11 have also been identified in Chinese and Indian patients with Fuchs dystrophy, the most common dystrophic cause of endothelial failure in the...

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“…Removal of the tectorial and Reissner's membranes and the stria vascularis improved probe access to the hair cells. Total RNA was obtained from freshly dissected cochleae and cochlear fractions using RNAlater and RNAqueous (Ambion, Austin, TX) (Morris et al, 2005). The organ of Corti was further dissected by separating the IHCand OHC-containing fragments at the tunnel of Corti.…”

Section: Methodsmentioning

confidence: 99%

Differential Expression of KCNQ4 in Inner Hair Cells and Sensory Neurons Is the Basis of Progressive High-Frequency Hearing Loss

Beisel¹,

Rocha-Sánchez²,

Morris³

et al. 2005

J. Neurosci.

113

109

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Human KCNQ4 mutations known as DFNA2 cause non-syndromic, autosomal-dominant, progressive high-frequency hearing loss in which the cellular and molecular basis is unclear. We provide immunofluorescence data showing that Kcnq4 expression in the adult cochlea has both longitudinal (base to apex) and radial (inner to outer hair cells) gradients. The most intense labeling is in outer hair cells at the apex and in inner hair cells as well as spiral ganglion neurons at the base. Spatiotemporal expression studies show increasing intensity of KCNQ4 protein labeling from postnatal day 21 (P21) to P120 mice that is most apparent in inner hair cells of the middle turn. We have identified four alternative splice variants of Kcnq4 in mice. The alternative use of exons 9 -11 produces three transcript variants (v1-v3), whereas the fourth variant (v4) skips all three exons; all variants have the same amino acid sequence at the C termini. Both reverse transcription-PCR and quantitative PCR analyses demonstrate that these variants have differential expression patterns along the length of the mouse organ of Corti and spiral ganglion neurons. Our expression data suggest that the primary defect leading to highfrequency loss in DFNA2 patients may be attributable to high levels of the dysfunctional Kcnq4_v3 variant in the spiral ganglion and inner hair cells in the basal hook region. Progressive hearing loss associated with aging may result from an increasing mutational load expansion toward the apex in inner hair cells and spiral ganglion neurons.

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Differential Expression of Genes within the Cochlea as Defined by a Custom Mouse Inner Ear Microarray

Cited by 37 publications

References 79 publications

Cochlear Function in Mice Lacking the BK Channel α, β1, or β4 Subunits

Cochlear Function in Mice Lacking the BK Channel α, β1, or β4 Subunits

Slc4a11 Gene Disruption in Mice

Differential Expression of KCNQ4 in Inner Hair Cells and Sensory Neurons Is the Basis of Progressive High-Frequency Hearing Loss

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