Abnormal mRNA splicing but normal auditory brainstem response (ABR) in mice with the prestin (SLC26A5) IVS2-2A > G mutation

Jian Zhang, Ziyi Liu, Aoshuang Chang, Jie Fang, Yuqin Men, Yong Tian, Xiaomei Ouyang, Denise Yan, Aizhen Zhang, Xiaoyang Sun, Jie Tang, Xue Z Liu, Jian Zuo, Jiangang Gao

Research output: Contribution to journalArticle

Abstract

Prestin is critical to OHC somatic motility and hearing sensitivity in mammals. Several mutations of the human SLC26A5 gene have been associated with deafness. However, whether the IVS2-2A > G mutation in the human SLC26A5 gene causes deafness remains controversial. In this study, we created a mouse model in which the IVS2-2A > G mutation was introduced into the mouse Slc26a5 gene by gene targeting. The homozygous Slc26a5 mutant mice were viable and fertile and displayed normal hearing sensitivity by ABR threshold analysis. Whole-mount immunostaining using prestin antibody demonstrated that prestin was correctly targeted to the lateral wall of OHCs, and no obvious hair cell loss occurred in mutant mice. No significant difference in the amount of prestin protein was observed between mutants and controls using western blot analysis. In OHCs isolated from mutants, the NLC was also normal. However, we observed a splicing abnormality in the Slc26a5 mRNA of the mutant mice. Eleven nucleotides were missing from the 5' end of exon 3 in Slc26a5 mRNA, but the normal ATG start codon in exon 3 was still detected. Thus, the IVS2-2A > G mutation in the Slc26a5 gene is insufficient to cause hearing loss in mice.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume790
DOIs
StatePublished - Aug 1 2016

Fingerprint

Brain Stem Auditory Evoked Potentials
Messenger RNA
Mutation
Deafness
Hearing
Genes
Exons
Initiator Codon
Gene Targeting
Alopecia
Hearing Loss
Mammals
Nucleotides
Western Blotting
Antibodies
Proteins

Keywords

  • ABR
  • Hearing loss
  • IVS2-2A > G
  • MRNA splicing
  • SLC26A5

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

Cite this

Abnormal mRNA splicing but normal auditory brainstem response (ABR) in mice with the prestin (SLC26A5) IVS2-2A > G mutation. / Zhang, Jian; Liu, Ziyi; Chang, Aoshuang; Fang, Jie; Men, Yuqin; Tian, Yong; Ouyang, Xiaomei; Yan, Denise; Zhang, Aizhen; Sun, Xiaoyang; Tang, Jie; Liu, Xue Z; Zuo, Jian; Gao, Jiangang.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 790, 01.08.2016, p. 1-7.

Research output: Contribution to journalArticle

Zhang, Jian ; Liu, Ziyi ; Chang, Aoshuang ; Fang, Jie ; Men, Yuqin ; Tian, Yong ; Ouyang, Xiaomei ; Yan, Denise ; Zhang, Aizhen ; Sun, Xiaoyang ; Tang, Jie ; Liu, Xue Z ; Zuo, Jian ; Gao, Jiangang. / Abnormal mRNA splicing but normal auditory brainstem response (ABR) in mice with the prestin (SLC26A5) IVS2-2A > G mutation. In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 2016 ; Vol. 790. pp. 1-7.
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abstract = "Prestin is critical to OHC somatic motility and hearing sensitivity in mammals. Several mutations of the human SLC26A5 gene have been associated with deafness. However, whether the IVS2-2A > G mutation in the human SLC26A5 gene causes deafness remains controversial. In this study, we created a mouse model in which the IVS2-2A > G mutation was introduced into the mouse Slc26a5 gene by gene targeting. The homozygous Slc26a5 mutant mice were viable and fertile and displayed normal hearing sensitivity by ABR threshold analysis. Whole-mount immunostaining using prestin antibody demonstrated that prestin was correctly targeted to the lateral wall of OHCs, and no obvious hair cell loss occurred in mutant mice. No significant difference in the amount of prestin protein was observed between mutants and controls using western blot analysis. In OHCs isolated from mutants, the NLC was also normal. However, we observed a splicing abnormality in the Slc26a5 mRNA of the mutant mice. Eleven nucleotides were missing from the 5' end of exon 3 in Slc26a5 mRNA, but the normal ATG start codon in exon 3 was still detected. Thus, the IVS2-2A > G mutation in the Slc26a5 gene is insufficient to cause hearing loss in mice.",
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AU - Fang, Jie

AU - Men, Yuqin

AU - Tian, Yong

AU - Ouyang, Xiaomei

AU - Yan, Denise

AU - Zhang, Aizhen

AU - Sun, Xiaoyang

AU - Tang, Jie

AU - Liu, Xue Z

AU - Zuo, Jian

AU - Gao, Jiangang

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AB - Prestin is critical to OHC somatic motility and hearing sensitivity in mammals. Several mutations of the human SLC26A5 gene have been associated with deafness. However, whether the IVS2-2A > G mutation in the human SLC26A5 gene causes deafness remains controversial. In this study, we created a mouse model in which the IVS2-2A > G mutation was introduced into the mouse Slc26a5 gene by gene targeting. The homozygous Slc26a5 mutant mice were viable and fertile and displayed normal hearing sensitivity by ABR threshold analysis. Whole-mount immunostaining using prestin antibody demonstrated that prestin was correctly targeted to the lateral wall of OHCs, and no obvious hair cell loss occurred in mutant mice. No significant difference in the amount of prestin protein was observed between mutants and controls using western blot analysis. In OHCs isolated from mutants, the NLC was also normal. However, we observed a splicing abnormality in the Slc26a5 mRNA of the mutant mice. Eleven nucleotides were missing from the 5' end of exon 3 in Slc26a5 mRNA, but the normal ATG start codon in exon 3 was still detected. Thus, the IVS2-2A > G mutation in the Slc26a5 gene is insufficient to cause hearing loss in mice.

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