Cochlear findings in the white spotting (Ws) rat

Hoshino, Tomoyuki; Mizuta, Kunihiro; Jing, Gao; Araki, Seiichi; Araki, Keisuke; Takeshita, Tamotsu; Wu, Rong; Morita, Hirofumi

doi:10.1016/s0378-5955(99)00192-6

Cited by 13 publications

(5 citation statements)

References 15 publications

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“…Subsequent electrophysiological studies indicate that a compartment within this lateral wall epithelium exhibits an electrochemical potential with respect to surrounding tissue and a low K ϩ concentration compared with those of an intracellular milieu and endolymph. Accordingly, these data point to the extracellular compartment of the intrastrial space as the site of highvoltage potential and identify basal and intermediate cells as the electrogenic cell population (Salt et al, 1987;Hoshino et al, 2000;Takeuchi et al, 2000;Marcus et al, 2002). Furthermore, the model posits that basal cell TJs are necessary to electrically isolate the intrastrial compartment.…”

Section: Discussionmentioning

confidence: 99%

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

Gow¹,

Davies

Southwood³

et al. 2004

J. Neurosci.

207

191

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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.

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Section: Discussionmentioning

confidence: 99%

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

Gow¹,

Davies

Southwood³

et al. 2004

J. Neurosci.

207

191

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“…KIT was activated through binding of KITLG , leading to autophosphorylation at tyrosine residues and downstream signaling cascade responses [ 41 ]. Previous studies have reported that several KIT variants at the tyrosine kinase domain have been identified in deaf rats and mice [ 42 , 43 ]. More importantly, Xu et al have confirmed that the KIT variant (NM_001044525.1, c.2418T > A, p.Asp806Glu) destroyed the development of melanocytes in the cochlea, which causes stria vascularis malformation and dysfunction, resulting in degeneration of HCs and finally hearing loss.…”

Section: Discussionmentioning

confidence: 99%

Deciphering potential causative factors for undiagnosed Waardenburg syndrome through multi-data integration

Sun,

Xiao,

et al. 2024

Orphanet J Rare Dis

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Background Waardenburg syndrome (WS) is a rare genetic disorder mainly characterized by hearing loss and pigmentary abnormalities. Currently, seven causative genes have been identified for WS, but clinical genetic testing results show that 38.9% of WS patients remain molecularly unexplained. In this study, we performed multi-data integration analysis through protein-protein interaction and phenotype-similarity to comprehensively decipher the potential causative factors of undiagnosed WS. In addition, we explored the association between genotypes and phenotypes in WS with the manually collected 443 cases from published literature. Results We predicted two possible WS pathogenic genes (KIT, CHD7) through multi-data integration analysis, which were further supported by gene expression profiles in single cells and phenotypes in gene knockout mouse. We also predicted twenty, seven, and five potential WS pathogenic variations in gene PAX3, MITF, and SOX10, respectively. Genotype-phenotype association analysis showed that white forelock and telecanthus were dominantly present in patients with PAX3 variants; skin freckles and premature graying of hair were more frequently observed in cases with MITF variants; while aganglionic megacolon and constipation occurred more often in those with SOX10 variants. Patients with variations of PAX3 and MITF were more likely to have synophrys and broad nasal root. Iris pigmentary abnormality was more common in patients with variations of PAX3 and SOX10. Moreover, we found that patients with variants of SOX10 had a higher risk of suffering from auditory system diseases and nervous system diseases, which were closely associated with the high expression abundance of SOX10 in ear tissues and brain tissues. Conclusions Our study provides new insights into the potential causative factors of WS and an alternative way to explore clinically undiagnosed cases, which will promote clinical diagnosis and genetic counseling. However, the two potential disease-causing genes (KIT, CHD7) and 32 potential pathogenic variants (PAX3: 20, MITF: 7, SOX10: 5) predicted by multi-data integration in this study are all computational predictions and need to be further verified through experiments in follow-up research.

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“…Viable homozygous W v mutant mice and W s (white spotting) rats have been shown to have interrupted developmental migration of neuronal crestderived melanocytes to the stria vascularis in the cochlea. This results in total or partial lack of strial intermediate cells and failure to generate a large endocochlear potential and subsequent deafness (Cable et al, 1992;Hoshino et al, 2000). It therefore seems that homozygosity for piebaldism in humans may result in deafness by a similar mechanism.…”

Section: Discussionmentioning

confidence: 99%

Homozygosity for piebaldism with a proven KIT mutation resulting in depigmentation of the skin and hair, deafness, developmental delay and autism spectrum disorder

Kilsby

Cruwys²,

Kukendrajah

et al. 2013

Clinical Dysmorphology

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Cochlear findings in the white spotting (Ws) rat

Cited by 13 publications

References 15 publications

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

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

Deciphering potential causative factors for undiagnosed Waardenburg syndrome through multi-data integration

Homozygosity for piebaldism with a proven KIT mutation resulting in depigmentation of the skin and hair, deafness, developmental delay and autism spectrum disorder

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