{'fraction_non_alphanumeric': 0.019166267369429803, 'fraction_numerical': 0.01581217057977959, 'mean_word_length': 5.5046728971962615, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
An L1 retrotransposon insertion–induced deafness mouse model for studying the development and function of the cochlear stria vascularis

Significance To gain better hearing sensitivity, the energetic and metabolic supplies are crucial for cochlea to develop a blood-labyrinth barrier containing abundant capillaries and cellular compartments. For example, the stria vascularis, the power plant of the cochlea, generates a +80 mV endocochlear potential and a 150 mM potassium concentration in the scala media. Previous studies of stria vascularis development and function have been largely focused on characterizing transcription factors, channels, and transporters. In our study, we identify a retrotransposon insertion mutation responsible for complete stria vascularis loss of function. Our study further highlights the diversity of genetic mutations capable of inducing inherited deafness. 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.