https://scholars.lib.ntu.edu.tw/handle/123456789/586659
標題: | Toward the Pathogenicity of the SLC26A4 p.C565Y Variant Using a Genetically Driven Mouse Model | 作者: | Hu, Chin-Ju Lu, Ying-Chang TING-HUA YANG Chan, Yen-Hui TIEN-CHEN LIU Yu, I-Shing SHU-WHA LIN Cheng, Yen-Fu Chen-Chi Wu Hsu, Chuan-Jen |
關鍵字: | Pendred syndrome; SLC26A4; human; mice; p.C565Y variant | 公開日期: | 10-三月-2021 | 卷: | 22 | 期: | 6 | 來源出版物: | International journal of molecular sciences | 摘要: | Recessive variants of the SLC26A4 gene are globally a common cause of hearing impairment. In the past, cell lines and transgenic mice were widely used to investigate the pathogenicity associated with SLC26A4 variants. However, discrepancies in pathogenicity between humans and cell lines or transgenic mice were documented for some SLC26A4 variants. For instance, the p.C565Y variant, which was reported to be pathogenic in humans, did not exhibit functional pathogenic consequences in cell lines. To address the pathogenicity of p.C565Y, we used a genotype-based approach in which we generated knock-in mice that were heterozygous (Slc26a4+/C565Y), homozygous (Slc26a4C565Y/C565Y), and compound heterozygous (Slc26a4919-2A>G/C565Y) for this variant. Subsequent phenotypic characterization revealed that mice with these genotypes demonstrated normal auditory and vestibular functions, and normal inner-ear morphology and pendrin expression. These findings indicate that the p.C565Y variant is nonpathogenic for mice, and that a single p.C565Y allele is sufficient to maintain normal inner-ear physiology in mice. Our results highlight the differences in pathogenicity associated with certain SLC26A4 variants between transgenic mice and humans, which should be considered when interpreting the results of animal studies for SLC26A4-related deafness. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/586659 | ISSN: | 16616596 | DOI: | 10.3390/ijms22062789 | SDG/關鍵字: | CRISPR associated endonuclease Cas9; pendrin; pentobarbital; Slc26a4 protein, mouse; animal experiment; animal model; animal tissue; Article; auditory threshold; clustered regularly interspaced short palindromic repeat; cochlea duct; cochlear hair cell; controlled study; endolymphatic sac; evoked brain stem auditory response; genetic variability; genotype; hearing; heterozygote; histology; homozygote; inner ear; male; morphology; mouse; nonhuman; pathogenicity; Pendred syndrome; phenotype; protein expression; recessive gene; stria vascularis; swimming; transgenic mouse; vestibular function; vestibule aqueduct; animal; C57BL mouse; disease model; genetic association study; genetic predisposition; genetics; human; knockout mouse; metabolism; mutation; pathology; perception deafness; physiology; procedures; Animals; Disease Models, Animal; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Hearing Loss, Sensorineural; Humans; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Mutation; Phenotype; Sulfate Transporters; Vestibular Aqueduct |
顯示於: | 醫學檢驗暨生物技術學系 |
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