Solute Carrier Family 26 Member a2 (slc26a2) Regulates Otic Development and Hair Cell Survival in Zebrafish

Fei Liu; Wenjun Xia; Jiongjiong Hu; Yingzhi Wang; Fan Yang; Shaoyang Sun; Jin Zhang; Nan Jiang; Huijun Wang; Weidong Tian; Xu Wang; Duan Ma

doi:10.1371/journal.pone.0136832

Solute Carrier Family 26 Member a2 (slc26a2) Regulates Otic Development and Hair Cell Survival in Zebrafish

PLoS One. 2015 Sep 16;10(9):e0136832. doi: 10.1371/journal.pone.0136832. eCollection 2015.

Authors

Fei Liu¹, Wenjun Xia², Jiongjiong Hu³, Yingzhi Wang¹, Fan Yang², Shaoyang Sun¹, Jin Zhang¹, Nan Jiang¹, Huijun Wang⁴, Weidong Tian⁵, Xu Wang¹, Duan Ma⁶

Affiliations

¹ Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Molecular Biology, Institute of Medical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
² Institutes of Biomedical Science, Fudan University, Shanghai, 200032, China.
³ Department of Otorhinolaryngology, Shanghai East Hospital, Tongji University, Shanghai, China.
⁴ Children's Hospital, Fudan University, Shanghai, 200032, China.
⁵ School of Life Sciences, Institute of Biostatistics, Fudan University, Shanghai, P.R. China.
⁶ Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Collaborative Innovation Center of Genetics and Development, Department of Biochemistry and Molecular Biology, Institute of Medical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China; Institutes of Biomedical Science, Fudan University, Shanghai, 200032, China.

Abstract

Hearing loss is one of the most prevalent human birth defects. Genetic factors contribute to the pathogenesis of deafness. It is estimated that one-third of deafness genes have already been identified. The current work is an attempt to find novel genes relevant to hearing loss using guilt-by-profiling and guilt-by-association bioinformatics analyses of approximately 80 known non-syndromic hereditary hearing loss (NSHL) genes. Among the 300 newly identified candidate deafness genes, slc26a2 were selected for functional studies in zebrafish. The slc26a2 gene was knocked down using an antisense morpholino (MO), and significant defects were observed in otolith patterns, semicircular canal morphology, and lateral neuromast distributions in morphants. Loss-of-function defects are caused primarily by apoptosis, and morphants are insensitive to sound stimulation and imbalanced swimming behaviours. Morphant defects were found to be partially rescued by co-injection of human SLC26A2 mRNA. All the results suggest that bioinformatics is capable of predicting new deafness genes and this showed slc26a2 is to be a critical otic gene whose dysfunction may induce hearing impairment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anion Transport Proteins / deficiency
Anion Transport Proteins / genetics
Anion Transport Proteins / metabolism*
Apoptosis
Cell Survival
Cilia
Computational Biology
Deafness / genetics
Deafness / metabolism
Deafness / physiopathology
Ear, Inner / growth & development
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Hair Cells, Auditory / cytology*
Hearing
Humans
Larva
Sulfate Transporters
Swimming
Zebrafish / embryology
Zebrafish / genetics
Zebrafish / metabolism*
Zebrafish Proteins / deficiency
Zebrafish Proteins / genetics
Zebrafish Proteins / metabolism*

Substances

Anion Transport Proteins
Slc26a2 protein, zebrafish
Sulfate Transporters
Zebrafish Proteins

Grants and funding

This study was supported by the East Raising Sun Talents Program of Shanghai East Hospital, Tongji University (2013DFYY-2), the Foundation for Development of Science and Technology, Pudong new district, Shanghai (2013PKJ2013-Y18), National Basic Research Program of China (2011CB504502), Basic Key Program of Shanghai Scientific and Technology Committee (14DJ1400103) and Program of Shanghai Municipal Commission of Health and Family Planning (2013ZYJB0015).