Loss of inner hair cell ribbon synapses and auditory nerve fiber regression in Cldn14 knockout mice

Claußen, Maike; Schulze, Jessika; Nothwang, Hans Gerd

doi:10.1016/j.heares.2020.107950

Cited by 3 publications

(3 citation statements)

References 38 publications

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“…To date, 14 pathogenic mutations have been associated with ARNSHL in humans, of which 9 are missense mutations, 3 are nonsense mutations and 1 is a frameshift deletion (Table 1). The phenotype associated with 9 of these variants has been reported, showing a greater degree of hearing loss severity at higher frequencies compared to lower frequencies, which correlates with the degeneration pattern reported in the knockout mouse where the apical region showed more pronounced hair cell degeneration and a more significant loss of presynaptic ribbons compared to the basal region [30]. In this report, it is noteworthy that all affected siblings display profound hearing loss across all frequencies.…”

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

“…Moreover, the Cldn14 knockout mice have shown the loss of ribbon synapses in inner hair cells and regression of auditory nerve fibers [30]. Given the important role of the auditory nerve in cochlear-implant-based auditory rehabilitation [32], Claußen et al proposed exploring the performance of cochlear implantation in Cldn14−/− mice in the future [30]. In the present study, the four deaf children with the c.202C>T (p.Arg68Ter) nonsense variant do not appear to exhibit defects in their auditory nerves, as their cochlear implants have successfully improved their hearing levels.…”

Section: Discussionmentioning

confidence: 99%

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The Segregation of p.Arg68Ter-CLDN14 Mutation in a Syrian Deaf Family, Phenotypic Variations, and Comparative Analysis with the GJB2 Gene

Tlili,

Mutery,

Chouchen

2024

Genes

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Hearing impairment, a rare inherited condition, is notably prevalent in populations with high rates of consanguinity. The most common form observed globally is autosomal recessive non-syndromic hearing loss. Despite its prevalence, this genetic disorder is characterized by a substantial genetic diversity, making diagnosis and screening challenging. The emergence of advanced next-generation sequencing (NGS) technologies has significantly advanced the discovery of genes and variants linked to various conditions, such as hearing loss. In this study, our objective was to identify the specific variant causing hearing loss in a family from Syria using clinical exome sequencing. The proband in the family exhibited profound deafness as shown by pure-tone audiometry results. The analysis of the different variants obtained by NGS revealed the presence of a nonsense mutation within the CLDN14 gene. Through Sanger sequencing, we verified that this variant segregates with the disease and was not present in the control population. Moreover, we conducted a comprehensive review of all reported deafness-related CLDN14 mutations and their associated phenotypes. Furthermore, we endeavored to carry out a comparative analysis between the CLDN14 and GJB2 genes, with the objective of identifying potential factors that could explain the notable discrepancy in mutation frequency between these two genes.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Segregation of p.Arg68Ter-CLDN14 Mutation in a Syrian Deaf Family, Phenotypic Variations, and Comparative Analysis with the GJB2 Gene

Tlili,

Mutery,

Chouchen

2024

Genes

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Molecular evolution of toothed whale genes reveals adaptations to echolocating in different environments

Magpali

Nery

Freitas

et al. 2023

Preprint

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Echolocation was a key development in toothed whale evolution, favoring their ecological success and adaptive radiation across multiple habitats, from shallow, murky rivers in South America to deep oceans in East Asia. Previous bioacoustic and morphological studies suggest that environmental pressures have influenced the evolution of echolocation in odontocetes. This hypothesis demands further investigation, especially regarding molecular mechanisms involved in odontocetes' adaptive radiation across multiple habitats. Here we show that the coding sequences of four hearing genes involved in echolocation (CDH23, SLC26A5, TMC1 and CLDN14) have different signatures of molecular evolution among riverine, coastal and oceanic dolphins, suggesting that the evolutionary constraints of these habitats have shaped the genetic diversity underlying toothed whale sonars. Our comparative analysis across 37 odontocete species has revealed patterns of accelerated evolution within coastal and riverine lineages, supporting the hypothesis that these habitats generate specific selective pressures to sonar propagation, which are not found in the ocean (e.g., clutter and reverberation). Specific branches with sites under diversifying selection include: three coastal/estuarine species which have recently diverged from closely-related lineages inhabiting freshwater (Cephalorhynchus commersonii, Sotalia guianensis and Orcaella heinsohni - CDH23), and three species that operate specialized Narrow Band High Frequency Sonars (Phocoena sinus - SLC26A5, Neophocaena phocaenoides and Cephalorhynchus commersonii - CDH23). All positively selected lineages are coastal or estuarine from shallow waters (< 100), corroborating current knowledge on these species' sonars. Among river dolphin branches, positive selection was found on specific sites of the genes CDH23 and SLC26A5, when compared to other cetaceans and Laurasiatherians. Finally, the detection of sites with different overall substitution rates (dN/dS) among river and marine dolphins, together with the finding of different amounts of positively selected sites in each environmental group, suggests distinct selective pressures acting in these groups in the molecular evolution of echolocation.

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Low‐intensity noise exposure takes an essential part in the mechanism of late‐onset hereditary hearing loss caused by Abcc1 mutation

Jiang,

Zhang,

Liu

et al. 2024

Clinical Genetics

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With the development of the social economy, we are exposed to increasing noise in our daily lives. Our previous work found an ABCC1(NM_004996.3:c.A1769G, NP_004987.2:p.N590S) variant which cosegregated with the patients in an autosomal dominant non‐syndromic hearing loss family. At present, the specific mechanism of deafness caused by ABCC1 mutation is still not clear. Using the knock‐in mouse model simulating human ABCC1 mutation, we found that the occurrence of family‐related phenotypes was likely attributed to the combination of the mouse genotype and low‐intensity noise. GSH and GSSG are important physiological substrates of ABCC1. The destruction of GSH‐GSSG balance in the cochleae of both Abcc1N591S/+ mice and Abcc1N591S/N591S mice during low‐intensity noise exposure may result in irreversible damage to the hair cells of the cochleae, consequently leading to hearing loss in mice. The findings offered a potential novel idea for the prevention and management of hereditary hearing loss within this family.

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Loss of inner hair cell ribbon synapses and auditory nerve fiber regression in Cldn14 knockout mice

Cited by 3 publications

References 38 publications

The Segregation of p.Arg68Ter-CLDN14 Mutation in a Syrian Deaf Family, Phenotypic Variations, and Comparative Analysis with the GJB2 Gene

The Segregation of p.Arg68Ter-CLDN14 Mutation in a Syrian Deaf Family, Phenotypic Variations, and Comparative Analysis with the GJB2 Gene

Molecular evolution of toothed whale genes reveals adaptations to echolocating in different environments

Low‐intensity noise exposure takes an essential part in the mechanism of late‐onset hereditary hearing loss caused by Abcc1 mutation

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