title: Solute Carrier Family 26 Member a2 (slc26a2) Regulates Otic Development and Hair Cell Survival in Zebrafish.
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.
authors.affiliation: 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.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Institutes of Biomedical Science, Fudan University, Shanghai, 200032, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Xia
authors.affiliation: Department of Otorhinolaryngology, Shanghai East Hospital, Tongji University, Shanghai, China.
authors.forename: Jiongjiong
authors.initials: J
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Yingzhi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institutes of Biomedical Science, Fudan University, Shanghai, 200032, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Shaoyang
authors.initials: S
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Children's Hospital, Fudan University, Shanghai, 200032, China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Institute of Biostatistics, Fudan University, Shanghai, P.R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Duan
authors.initials: D
authors.lastname: Ma
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D002470:Cell Survival; D002923:Cilia; D019295:Computational Biology; D003638:Deafness / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007758:Ear, Inner / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006198:Hair Cells, Auditory / Q000166:cytology*; D006309:Hearing; D006801:Humans; D007814:Larva; D000076988:Sulfate Transporters; D013550:Swimming; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D027321:Anion Transport Proteins; C000608099:Slc26a2 protein, zebrafish; D000076988:Sulfate Transporters; D029961:Zebrafish Proteins