title: Abnormal mRNA splicing but normal auditory brainstem response (ABR) in mice with the prestin (SLC26A5) IVS2-2A>G mutation.
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.
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Aoshuang
authors.initials: A
authors.lastname: Chang
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Fang
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Men
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Otolaryngology, University of Miami, Miami, FL 33136, USA.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Ouyang
authors.affiliation: Department of Otolaryngology, University of Miami, Miami, FL 33136, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Yan
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.
authors.forename: Aizhen
authors.initials: A
authors.lastname: Zhang
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Physiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Otolaryngology, University of Miami, Miami, FL 33136, USA. Electronic address: xliu@med.miami.edu.
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: jian.zuo@stjude.org.
authors.forename: Jian
authors.initials: J
authors.lastname: Zuo
authors.affiliation: School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, Jinan 250100, China. Electronic address: jggao@sdu.edu.cn.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000235:genetics*; D005260:Female; D055879:Gene Knock-In Techniques; D034381:Hearing Loss / Q000235:genetics*; D008297:Male; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D020409:Molecular Motor Proteins / Q000235:genetics*; D009154:Mutation; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D020409:Molecular Motor Proteins; C498720:Pres protein, mouse; D012333:RNA, Messenger
keywords: ABR; Hearing loss; IVS2-2A>G; SLC26A5; mRNA splicing