{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T01:03:45Z","timestamp":1788051825027,"version":"build-2784847793"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82222016"],"award-info":[{"award-number":["82222016"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82350005"],"award-info":[{"award-number":["82350005"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mutations in AIFM1, encoding for apoptosis-inducing factor (AIF), cause AUNX1, an X-linked neurologic disorder with late-onset auditory neuropathy (AN) and peripheral neuropathy. Despite significant research on AIF, there are limited animal models with the disrupted AIFM1 representing the corresponding phenotype of human AUNX1, characterized by late-onset hearing loss and impaired auditory pathways. Here, we generated an Aifm1 p.R450Q knock-in mouse model (KI) based on the human AIFM1 p.R451Q mutation. Hemizygote KI male mice exhibited progressive hearing loss from P30 onward, with greater severity at P60 and stabilization until P210. Additionally, muscle atrophy was observed at P210. These phenotypic changes were accompanied by a gradual reduction in the number of spiral ganglion neuron cells (SGNs) at P30 and ribbons at P60, which coincided with the translocation of AIF into the nucleus starting from P21 and P30, respectively. The SGNs of KI mice at P210 displayed loss of cytomembrane integrity, abnormal nuclear morphology, and dendritic and axonal demyelination. Furthermore, the inner hair cells and myelin sheath displayed abnormal mitochondrial morphology, while fibroblasts from KI mice showed impaired mitochondrial function. In conclusion, we successfully generated a mouse model recapitulating AUNX1. Our findings indicate that disruption of Aifm1 induced the nuclear translocation of AIF, resulting in the impairment in the auditory pathway.<\/jats:p>","DOI":"10.1093\/hmg\/ddae010","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T04:38:32Z","timestamp":1709786312000},"page":"905-918","source":"Crossref","is-referenced-by-count":5,"title":["AIF translocation into nucleus caused by <i>Aifm1<\/i> R450Q mutation: generation and characterization of a mouse model for AUNX1"],"prefix":"10.1093","volume":"33","author":[{"given":"Tao","family":"Shi","sequence":"first","affiliation":[{"name":"Senior Department of Otolaryngology-Head and Neck Surgery, the Sixth Medical Center of PLA General Hospital, Medical School of Chinese PLA , 6 Fucheng Road, Beijing 100048 , P. R. China"},{"name":"National Clinical Research Center for Otolaryngologic Diseases, Chinese PLA General Hospital , 6 Fucheng Road, Beijing 100048 , P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Senior Department of Otolaryngology-Head and Neck Surgery, the Sixth Medical Center of PLA General Hospital, Medical School of Chinese PLA , 6 Fucheng Road, Beijing 100048 , P. R. China"},{"name":"National Clinical Research Center for Otolaryngologic Diseases, Chinese PLA General Hospital , 6 Fucheng Road, Beijing 100048 , P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[{"name":"Senior Department of Otolaryngology-Head and Neck Surgery, the Sixth Medical Center of PLA General Hospital, Medical School of Chinese PLA , 6 Fucheng Road, Beijing 100048 , P. R. China"},{"name":"National Clinical Research Center for Otolaryngologic Diseases, Chinese PLA General Hospital , 6 Fucheng Road, Beijing 100048 , P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Senior Department of Otolaryngology-Head and Neck Surgery, the Sixth Medical Center of PLA General Hospital, Medical School of Chinese PLA , 6 Fucheng Road, Beijing 100048 , P. R. China"},{"name":"National Clinical Research Center for Otolaryngologic Diseases, Chinese PLA General Hospital , 6 Fucheng Road, Beijing 100048 , P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3604-7279","authenticated-orcid":false,"given":"Qiuju","family":"Wang","sequence":"additional","affiliation":[{"name":"Senior Department of Otolaryngology-Head and Neck Surgery, the Sixth Medical Center of PLA General Hospital, Medical School of Chinese PLA , 6 Fucheng Road, Beijing 100048 , P. R. China"},{"name":"National Clinical Research Center for Otolaryngologic Diseases, Chinese PLA General Hospital , 6 Fucheng Road, Beijing 100048 , P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,6]]},"reference":[{"key":"2024050512562887400_ref1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1055\/s-2002-34456","article-title":"Identification of auditory neuropathy in infants and children","volume":"23","author":"Sininger","year":"2002","journal-title":"Semin Hear"},{"key":"2024050512562887400_ref2","doi-asserted-by":"crossref","first-page":"3141","DOI":"10.1093\/brain\/awv270","article-title":"Pathophysiological mechanisms and functional hearing consequences of auditory neuropathy","volume":"138","author":"Rance","year":"2015","journal-title":"Brain J Neurol"},{"key":"2024050512562887400_ref3","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1093\/brain\/119.3.741","article-title":"Auditory neuropathy","volume":"119","author":"Starr","year":"1996","journal-title":"Brain J 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