A Point Mutation in the Gene for Asparagine-Linked Glycosylation 10B (Alg10b) Causes Nonsyndromic Hearing Impairment in Mice (Mus musculus)

Abstract

The study of mouse hearing impairment mutants has led to the identification of a number of human hearing impairment genes and has greatly furthered our understanding of the physiology of hearing. The novel mouse mutant neurological/sensory 5 (nse5) demonstrates a significantly reduced or absent startle response to sound and is therefore a potential murine model of human hearing impairment. Genetic analysis of 500 intercross progeny localized the mutant locus to a 524 kilobase (kb) interval on mouse chromosome 15. A missense mutation in a highly-conserved amino acid was found in the asparagine-linked glycosylation 10B gene (Alg10b), which is within the critical interval for the nse5 mutation. A 20.4 kb transgene containing a wildtype copy of the Alg10b gene rescued the mutant phenotype in nse5/nse5 homozygous animals, confirming that the mutation in Alg10b is responsible for the nse5/nse5 mutant phenotype. Homozygous nse5/nse5 mutants had abnormal auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), and cochlear microphonics (CMs). Endocochlear potentials (EPs), on the other hand, were normal. ABRs and DPOAEs also confirmed the rescue of the mutant nse5/nse5 phenotype by the wildtype Alg10b transgene. These results suggested a defect in the outer hair cells of mutant animals, which was confirmed by histologic analysis. This is the first report of mutation in a gene involved in the asparagine (N)-linked glycosylation pathway causing nonsyndromic hearing impairment, and it suggests that the hearing apparatus, and the outer hair cells in particular, are exquisitely sensitive to perturbations of the N-linked glycosylation pathway.

Correlation analysis of European Sea Bass (Dicentrarchus labrax) Growth Hormone (GH) Gene and Growth Traits

“…In the present work, two nonsynonymous (L8S and S28T) amino acid substitutions were determined compared to the native GH protein. L8S may have in uenced the 3D structure of the GH because leucine is relatively and non-polar amino acid, whereas serine is smaller and more polar amino acid (Probst et al, 2013). In literature, some studies have been reported on the replacement of the leucine with serine amino acid which causes a signi cant result, thereby probably signi cant change of the 3D structure of the proteins (Probst et al, 2013;Sürmeli et al, 2019Sürmeli et al, , 2022.…”

“…L8S may have in uenced the 3D structure of the GH because leucine is relatively and non-polar amino acid, whereas serine is smaller and more polar amino acid (Probst et al, 2013). In literature, some studies have been reported on the replacement of the leucine with serine amino acid which causes a signi cant result, thereby probably signi cant change of the 3D structure of the proteins (Probst et al, 2013;Sürmeli et al, 2019Sürmeli et al, , 2022. Therefore, variation depending on its new function may be eliminated from the population in the next generations.…”

Prenatal Diagnosis and Molecular Cytogenetic Characterization of Copy Number Variations on 4p15.2p16.3, Xp22.31, and 12p11.1q11 in a Fetus with Ultrasound Anomalies: A Case Report and Literature Review

“…ALG10 (OMIM: 618355), encoding a membrane-associated protein, might be associated with nonsyndromic hearing impairment in mice. Currently, there is no pathogenic evidence on ALG10 duplication [33].…”

Functional implications of Cav2.3 R‐type voltage‐gated calcium channels in the murine auditory system – novel vistas from brainstem‐evoked response audiometry

“…In this study, we used an automated threshold detection based on previous publications (Alvarado, Fuentes‐Santamaria, Gabaldon‐Ull, Blanco, & Juiz, ; Bogaerts, Clements, Sullivan, & Oleskevich, ; Probst et al, ). Software "R" (The R Foundation, version 3.2.1, R Core Team 2015) was combined with the additional packages “reshape2” (version 1.4.1), “ggplot2” (version 1.0.1), “data.table” (version 1.9.4), “gdata” (version 2.13.3), “pastecs” (version 1.3.18), “waveslim” (version 1.7.5) and “MassSpecWavelet” (version 1.30.0; Du, Kibbe, & Lin, ) for data processing and analysis.…”