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Results show GRAIL deficiency reduces threshold elevation, hair cell loss, synaptic ribbon loss, and noise-driven gene expression 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is the main purpose of the study on GRAIL knockout mice?","Question",{"text":63,"@type":64},"To determine whether GRAIL deficiency protects against aging-related and noise-induced hearing loss and to identify associated molecular changes.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How were hearing function and cochlear cellular changes evaluated?",{"text":68,"@type":64},"Hearing was measured using auditory brainstem response, while cochlear hair cells and synaptic ribbons were assessed via immunofluorescence staining.",{"name":70,"@type":61,"acceptedAnswer":71},"What key findings were observed in GRAIL knockout mice after noise exposure?",{"text":72,"@type":64},"GRAIL knockout mice showed significantly less elevation in hearing threshold and less loss of outer hair cells and synaptic ribbons compared with wild-type mice.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},436312,1790766027,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & 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\nGRAIL gene knockout mice protect against agingrelated and noise-induced hearing loss  \nKai-Fen Chuanga, Chih-Hung Wanga,b,c, Hang-Kang Chena, Yuan-Yung Lina,b, Chia-Hsin Lina, Yi-Chun Lina, Cheng-Ping Shiha, Chao-Yin Kuoa, Ying-Chuan Chend,* , Hsin-Chien Chena,*  \naDepartment of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC; bGraduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC; cDivision of Otolaryngology, Taipei Veterans General Hospital, Taoyuan Branch, Taoyuan, Taiwan; dDepartment of Physiology & Biophysics, National Defense Medical Center, Taipei, Taiwan, ROC  \nAbstract  \nBackground: Hearing loss is a global health issue and its etiopathologies involve complex molecular pathways. The ubiquitinproteasome system has been reported to be associated with cochlear development and hearing loss. The gene related to anergyin lymphocytes (GRAIL), as an E3 ubiquitin ligase, has not, as yet, been examined in aging-related and noise-induced hearing loss mice models.  \nMethods: This study used wild-type (WT) and GRAIL knockout (KO) mice to examine cochlear hair cells and synaptic ribbons using immunofluorescence staining. The hearing in WT and KO mice was detected using auditory brainstem response. Gene expression patterns were compared using RNA-sequencing to identify potential targets during the pathogenesis of noise-induced hearing loss in WT and KO mice.  \nResults: At the 12-month follow-up, GRAIL KO mice had significantly less elevation in threshold level and immunofluorescence staining showed less loss of outer hair cells and synaptic ribbons in the hook region compared with GRAIL WT mice. At days 1, 14, and 28 after noise exposure, GRAIL KO mice had significantly less elevation in threshold level than WT mice. After noise exposure, GRAIL KO mice showed less loss of outer hair cells in the cochlear hook and basal regions compared with WT mice. Moreover, immunofluorescence staining showed less loss of synaptic ribbons in the hook regions of GRAIL KO mice than of WT mice. RNAseq analysis results showed significant differences in C-C motif chemokine ligand 19 (CCL19), C-C motif chemokine ligand 21 (CCL21), interleukin 25 (IL25), glutathione peroxidase 6 (GPX6), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (NOX1) genes after noise exposure.  \nConclusion: The present data demonstrated that GRAIL deficiency protects against aging-related and noise-induced hearing loss. The mechanism involved needs to be further clarified from the potential association with synaptic modulation, inflammation, and oxidative stress.  \nKeywords: Aging; Cochlea; GRAIL; Hearing loss; Noise; RNF128; Ubiquitin-proteasome system  \n1. INTRODUCTION  \nHearing loss affects over 20% of the world’s population. The annual additional investment attributed to hearing care amounted to US$ 750 billion, especially in low- and middleincome countries.1 The term sensorineural hearing loss (SNHL) refers to problems that involve transmission at and after the  \n* Address correspondence. Dr. Ying-Chuan Chen, Department of Physiology & Biophysics, National Defense Medical Center, Tri-Service General Hospital, 161, Section 6, Ming-Chun East Road, Taipei 114, Taiwan, ROC. E-mail address: [addy0918@gmail.com](addy0918@gmail.com) (Y.-C. Chen); Dr. Hsin-Chien Chen, Department of Otolaryngology-Head and Neck Surgery, Tri-service General Hospital, National Defense Medical Center, 325, Section 2, Cheng-Kung Road, Taipei 114, Taiwan, [ROC. E-mail address: acolufreia@yahoo.com.tw](ROC. E-mail address: acolufreia@yahoo.com.tw) (H.-C. Chen).  \nConflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article.  \nJournal of Chinese Medical Association. (2023) 86: 1101-1108.  \nReceived May 11, 2023; accepted September 9, 2023. doi: 10. 1097/J","cbCairvlNJmTSk4K","https://ap.wps.com/l/cbCairvlNJmTSk4K","pdf",920565,"English","# INTRODUCTION\n## Hearing loss overview and common etiologies\n## Molecular hypotheses of sensorineural hearing loss\n# METHODS\n## Animal models and experimental design\n## Immunofluorescence and auditory brainstem response\n## RNA-sequencing for gene expression comparisons\n# RESULTS\n## Outcomes at 12-month follow-up\n## Outcomes after noise exposure across time points\n## Differential gene expression after noise exposure\n# CONCLUSION\n## Protective effect of GRAIL deficiency and proposed mechanisms","[{\"question\":\"What is the main purpose of the study on GRAIL knockout mice?\",\"answer\":\"To determine whether GRAIL deficiency protects against aging-related and noise-induced hearing loss and to identify associated molecular changes.\"},{\"question\":\"How were hearing function and cochlear cellular changes evaluated?\",\"answer\":\"Hearing was measured using auditory brainstem response, while cochlear hair cells and synaptic ribbons were assessed via immunofluorescence staining.\"},{\"question\":\"What key findings were observed in GRAIL knockout mice after noise exposure?\",\"answer\":\"GRAIL knockout mice showed significantly less elevation in hearing threshold and less loss of outer hair cells and synaptic ribbons compared with wild-type mice.\"}]","GRAIL gene knockout mice protect against aging-related and noise-induced hearing loss | PDF",1790677567]