Open AccessAn L1 retrotransposon insertion–induced deafness mouse model for studying the development and function of the cochlear stria vascularis
Author(s) -
Chengkun Song,
Jie Li,
Shuang Liu,
Hanqing Hou,
Tong Zhu,
Jiaofeng Chen,
Lian Liu,
Yichang Jia,
Wei Xiong
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2107933118
Subject(s) - endocochlear potential , cochlear duct , cochlea , mutant , retrotransposon , inner ear , biology , homeostasis , microbiology and biotechnology , hearing loss , genetics , medicine , anatomy , transposable element , gene , audiology
Dysregulation of ion and potential homeostasis in the scala media is the most prevalent cause of hearing loss in mammals. However, it is not well understood how the development and function of the stria vascularis regulates this fluid homeostasis in the scala media. From a mouse genetic screen, we characterize a mouse line, named 299 , that displays profound hearing impairment. Histology suggests that 299 mutant mice carry a severe, congenital structural defect of the stria vascularis. The in vivo recording of 299 mice using double-barreled electrodes shows that endocochlear potential is abolished and potassium concentration is reduced to ∼20 mM in the scala media, a stark contrast to the +80 mV endocochlear potential and the 150 mM potassium concentration present in healthy control mice. Genomic analysis revealed a roughly 7-kb-long, interspersed nuclear element (LINE-1 or L1) retrotransposon insertion on chromosome 11. Strikingly, the deletion of this L1 retrotransposon insertion from chromosome 11 restored the hearing of 299 mutant mice. In summary, we characterize a mouse model that enables the study of stria vascularis development and fluid homeostasis in the scala media.