Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 40, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2107933118
Keywords
deafness; stria vascularis; endocochlear potential; retrotransposon; LINE-1
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Funding
- National Natural Science Foundation of China [31522025, 31571080, 81873703, 31861163003]
- Beijing Municipal Science and Technology Commission [Z181100001518001]
- Tsinghua-Peking Center for Life Sciences
- Open Collaborative Research Program of Chinese Institute for Brain Research [2020-NKX-XM-04]
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Dysregulation of ion and potential homeostasis in the scala media is a common cause of hearing loss in mammals. A mouse genetic screen identified a mouse line, 299, with profound hearing impairment and a severe, congenital structural defect of the stria vascularis. Deleting a LINE-1 retrotransposon insertion on chromosome 11 restored hearing in these mutant mice, providing a new model for studying fluid homeostasis in the scala media.
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 similar 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.
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