Deafness in<i>Claudin 11</i>-Null Mice Reveals the Critical Contribution of Basal Cell Tight Junctions to Stria Vascularis Function

Gow, Alexander; Davies, Caroline; Southwood, Cherie M.; Frolenkov, Gregory I.; Chrustowski, Mark; Ng, Lily; Yamauchi, Daisuke; Marcus, Daniel C.; Kachar, Bechara

doi:10.1523/jneurosci.1640-04.2004

Cited by 209 publications

(202 citation statements)

References 45 publications

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“…Thus, it appears that while hair cells can tolerate some degree of EP reduction, an 18 mV EP or more is needed for the survival of OHCs. The fact that no hair cell pathology was observed in Claudin 11-null mice [47] when the EP was reduced to 30 mV also supports our conclusion that hair cells can tolerate some degree of EP reduction. The EP is never developed in Mitf -mutant mice, consistent with a previous study which showed that no intermediate cells were ever present in Mitf -mutant homozygous mice [16].…”

Section: Discussionsupporting

confidence: 79%

Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

Liu

Chen

et al. 2016

PLoS ONE

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Cochlear hair cells and the stria vascularis are critical for normal hearing. Hair cells transduce mechanical stimuli into electrical signals, whereas the stria is responsible for generating the endocochlear potential (EP), which is the driving force for hair cell mechanotransduction. We questioned whether hair cells and the stria interdepend for survival by using two mouse models. Atoh1 conditional knockout mice, which lose all hair cells within four weeks after birth, were used to determine whether the absence of hair cells would affect function and survival of stria. We showed that stria morphology and EP remained normal for long time despite a complete loss of all hair cells. We then used a mouse model that has an abnormal stria morphology and function due to mutation of the Mitf gene to determine whether hair cells are able to survive and transduce sound signals without a normal electrochemical environment in the endolymph. A strial defect, reflected by missing intermediate cells in the stria and by reduction of EP, led to systematic outer hair cell death from the base to the apex after postnatal day 18. However, an 18-mV EP was sufficient for outer hair cell survival. Surprisingly, inner hair cell survival was less vulnerable to reduction of the EP. Our studies show that normal function of the stria is essential for adult outer hair cell survival, while the survival and normal function of the stria vascularis do not depend on functional hair cells.

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Section: Discussionsupporting

confidence: 79%

Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

Liu

Chen

et al. 2016

PLoS ONE

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“…the results of the functional assays suggest a role for claudin-11 in maintaining tissue barriers, in accord with other reports. thus, claudin-11 null mice demonstrated hind limb weakness with slowed nerve conduction, impaired spermatogenesis and hearing loss as a result of impaired tissue barrier function (24,25). this study is limited by the use of a small number of bladder tissue samples.…”

Section: Discussionmentioning

confidence: 93%

Claudin-11 decreases the invasiveness of bladder cancer cells

Awsare

Martin²,

Haynes³

et al. 2011

Oncol Rep

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Abstract. the expression of claudin-11 in benign and malignant bladder tissue and the effect of forced expression of claudin-11 on tight junction function and invasiveness of bladder cancer cells were studied. claudin-11 expression was tested in bladder cancer cell lines (t24/83, rt 112/84 and eJ138) using reverse transcription-polymerase chain reaction (rt-pcr) and in benign and malignant bladder tissue by quantitative rt-pcr and immunohistochemistry. t24/83 cells were transfected with the pcDnA.1/nt-gFptopo vector containing full-length human claudin-11 sequence. stable-transfected cells overexpressing claudin-11 (t24 cl-11ex ), wild-type cells (t24 Wt ) and the empty plasmid control clone (t24 gFp ) were compared using transurothelial resistance (tUr), in vitro adhesion, invasion and growth assays. claudin-11 was strongly expressed in the non-invasive rt112/84 cell line compared to the invasive t24/83 and eJ138 tcc cell lines. Benign bladder tissue demonstrated equal expression of claudin-11 mrnA as carcinoma, but displayed more intense staining than malignant tissue on immunohistochemistry. Forced-expression of claudin-11 in t24/83 cells was confirmed by PCR, immunoprecipitation and by immunofluorescence, which demonstrated increased perinuclear claudin-11 staining. Forced expression of claudin-11 did not affect tUr (p=0.243), but significantly reduced invasion (p=0.001) while increasing cell matrix adhesion (p=0.001) and growth rates (p=0.001). the greater expression of claudin-11 in benign vs. malignant tissue and non-invasive vs. invasive cell lines, and its effect in reducing bladder cancer cell invasiveness suggests that claudin-11 may have a role in preventing cancer progression and may serve as a therapeutic target in reducing metastasis.

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“…At least five mice from each genotype were analyzed at each time point. Auditory brainstem responses (ABRs) were evoked in the left and right ears of avertin-anesthetized mice (0.375 mg/gm) with 2048 pure tone stimuli at 8, 16, and 32 kHz between 80 and 50 dB sound pressure level (SPL) at a rate of 29.1/sec and analyzed using Intelligent Hearing Systems equipment (Miami, FL) with minor modifications (Gow et al, 2004) from published methods (Zheng et al, 1999). Peak V latencies were normalized by subtracting peak I latencies (i.e., peak V Ϫ I) to correct for age-and stimulation frequency-dependent changes that otherwise increase variability in the EEG data.…”

Section: Methodsmentioning

confidence: 99%

“…To determine whether the rotarod phenotype might be associated with changes in conduction velocity in the CNS of Nkx6-2 null mice, we examined evoked potentials derived from ABRs in a manner similar to that of previous studies (Fujiyoshi et al, 1994;Gow et al, 2004). Presentation of 102 sec pure tone pips into the auditory canals of anesthetized mice at different sound pressure levels elicits a series of EEGs comprising five or six well resolved peaks with latencies ϳ1 msec apart (Fig.…”

Section: Nkx6-2 Null Mice Exhibit Motor Coordination and Cnsevoked Pomentioning

confidence: 99%

CNS Myelin Paranodes Require Nkx6-2 Homeoprotein Transcriptional Activity for Normal Structure

Southwood

Garbern

et al. 2004

J. Neurosci.

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Homeodomain proteins play critical roles during development in cell fate determination and proliferation, but few studies have defined gene regulatory networks for this class of transcription factors in differentiated cells. Using a lacZ-knock-in strategy to ablate Nkx6-2, we find that the Nkx6-2 promoter is active embryonically in neuroblasts and postnatally in oligodendrocytes. In addition to neurological deficits, we find widespread ultrastructural abnormalities in CNS white matter and aberrant expression of three genes encoding a paranodal microtubule destabilizing protein, stathmin 1, and the paranodal cell adhesion molecules neurofascin and contactin. The involvement of these downstream proteins in cytoskeletal function and cell adhesion reveals mechanisms whereby Nkx6-2 directly or indirectly regulates axon-glial interactions at myelin paranodes. Nkx6-2 does not appear to be the central regulator of axoglial junction assembly; nonetheless, our data constitute the first evidence of such a regulatory network and provide novel insights into the mechanism and effector molecules that are involved.

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Deafness inClaudin 11-Null Mice Reveals the Critical Contribution of Basal Cell Tight Junctions to Stria Vascularis Function

Cited by 209 publications

References 45 publications

Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

Organ of Corti and Stria Vascularis: Is there an Interdependence for Survival?

Claudin-11 decreases the invasiveness of bladder cancer cells

CNS Myelin Paranodes Require Nkx6-2 Homeoprotein Transcriptional Activity for Normal Structure

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