{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["12(3)"],"submitter":["Abu-Diab A"],"pubmed_abstract":["<h4>Purpose</h4>Usher syndrome (USH) is the most common syndromic inherited retinal disease, causing retinitis pigmentosa and sensorineural hearing loss. We reported previously that a nonsense mutation in the centrosome-associated protein CEP250 gene (encoding C-Nap1) causes atypical USH in patients of Iranian Jewish origin. To better characterize CEP250, we aimed to generate and study a knockout (KO) mouse model for Cep250.<h4>Methods</h4>Mice heterozygous for a \"knockout-first\" Cep250 construct were generated and bred with Cre recombinase mice to generate the null allele and produce homozygous Cep250 KO mice. Retinal function was evaluated by full-field electroretinography (ffERG) at variable ages, and retinal structure changes were examined using histological analysis. Hearing thresholds were detected using auditory brainstem response (ABR) at the age of 20 months.<h4>Results</h4>The Cep250 KO mouse model was generated by activating a construct harboring a deletion of exons 6 and 7. At 6 months, the ffERG was normal, but it decreased gradually with age. For both photopic and scotopic ffERG responses, very low amplitudes were evident at 20 months. Histological analysis confirmed late-onset retinal degeneration. ABR tests illustrated that hearing threshold significantly increased at the age of 20 months.<h4>Conclusions</h4>Although most USH animal models have normal retinal function and structure, the Cep250 KO mouse model shows both retinal degeneration and hearing loss with a relatively late age of onset. This model may shed more light on CEP250-associated retinal and hearing deficits and represents an efficient platform for the development of treatment modalities for USH.<h4>Translational relevance</h4>Our study demonstrates better understanding of Cep250-associated retinal and hearing disease in a mouse model and may help in developing more efficient gene therapy modalities."],"journal":["Translational vision science & technology"],"pagination":["3"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9987170"],"repository":["biostudies-literature"],"pubmed_title":["Homozygous Knockout of Cep250 Leads to a Relatively Late-Onset Retinal Degeneration and Sensorineural Hearing Loss in Mice."],"pmcid":["PMC9987170"],"pubmed_authors":["Salameh M","Matsevich C","Sharon D","Gopalakrishnan P","Gross M","de Jong M","Obolensky A","Abu-Diab A","Khateb S","Banin E","Ejzenberg A","Khalaileh A"],"additional_accession":[]},"is_claimable":false,"name":"Homozygous Knockout of Cep250 Leads to a Relatively Late-Onset Retinal Degeneration and Sensorineural Hearing Loss in Mice.","description":"<h4>Purpose</h4>Usher syndrome (USH) is the most common syndromic inherited retinal disease, causing retinitis pigmentosa and sensorineural hearing loss. We reported previously that a nonsense mutation in the centrosome-associated protein CEP250 gene (encoding C-Nap1) causes atypical USH in patients of Iranian Jewish origin. To better characterize CEP250, we aimed to generate and study a knockout (KO) mouse model for Cep250.<h4>Methods</h4>Mice heterozygous for a \"knockout-first\" Cep250 construct were generated and bred with Cre recombinase mice to generate the null allele and produce homozygous Cep250 KO mice. Retinal function was evaluated by full-field electroretinography (ffERG) at variable ages, and retinal structure changes were examined using histological analysis. Hearing thresholds were detected using auditory brainstem response (ABR) at the age of 20 months.<h4>Results</h4>The Cep250 KO mouse model was generated by activating a construct harboring a deletion of exons 6 and 7. At 6 months, the ffERG was normal, but it decreased gradually with age. For both photopic and scotopic ffERG responses, very low amplitudes were evident at 20 months. Histological analysis confirmed late-onset retinal degeneration. ABR tests illustrated that hearing threshold significantly increased at the age of 20 months.<h4>Conclusions</h4>Although most USH animal models have normal retinal function and structure, the Cep250 KO mouse model shows both retinal degeneration and hearing loss with a relatively late age of onset. This model may shed more light on CEP250-associated retinal and hearing deficits and represents an efficient platform for the development of treatment modalities for USH.<h4>Translational relevance</h4>Our study demonstrates better understanding of Cep250-associated retinal and hearing disease in a mouse model and may help in developing more efficient gene therapy modalities.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Mar","modification":"2025-05-18T12:55:18.996Z","creation":"2025-05-18T12:55:18.996Z"},"accession":"S-EPMC9987170","cross_references":{"pubmed":["36857066"],"doi":["10.1167/tvst.12.3.3"]}}