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Although mutations in each subunit of TRiC\/CCT are associated with various human neurodegenerative diseases, their impact in mammalian models has not yet been examined. A compound heterozygous mutation in <jats:italic>CCT2<\/jats:italic> (p.[Thr400Pro]; p.[Arg516His]) is causal for Leber congenital amaurosis. Here, we generate mice carrying each mutation and show that Arg516His (R516H) homozygosity causes photoreceptor degeneration accompanied by a significant depletion of TRiC\/CCT substrate proteins in the retina. In contrast, Thr400Pro (T400P) homozygosity results in embryonic lethality, and the compound heterozygous mutant (T400P\/R516H) mouse showed aberrant cone cell lamination and died 2 weeks after birth. Finally, CCDC181 is identified as a interacting protein for CCT\u03b2 protein, and its localization to photoreceptor connecting cilia is compromised in the mutant mouse. Our results demonstrate the distinct impact of each mutation in vivo and suggest a requirement for CCT\u03b2 in ciliary maintenance.<\/jats:p>","DOI":"10.1038\/s42003-024-06384-2","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T13:05:55Z","timestamp":1717419955000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Compound heterozygous mutations in a mouse model of Leber congenital amaurosis reveal the role of CCT2 in photoreceptor maintenance"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6609-2647","authenticated-orcid":false,"given":"Akiko","family":"Suga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuriko","family":"Minegishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9066-4959","authenticated-orcid":false,"given":"Koji","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1447-0081","authenticated-orcid":false,"given":"Takeshi","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,3]]},"reference":[{"key":"6384_CR1","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1016\/j.cell.2015.09.053","volume":"163","author":"MY Hein","year":"2015","unstructured":"Hein, M. 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Uncovering the genetic lesions underlying the most severe form of Hirschsprung disease by whole-genome sequencing. Eur. J. Hum. Genet. 26, 818\u2013826 (2018).","journal-title":"Eur. J. Hum. Genet."},{"key":"6384_CR9","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1136\/jmg.2005.039230","volume":"43","author":"A Bouhouche","year":"2006","unstructured":"Bouhouche, A., Benomar, A., Bouslam, N., Chkili, T. & Yahyaoui, M. Mutation in the epsilon subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct5) gene causes autosomal recessive mutilating sensory neuropathy with spastic paraplegia. J. Med. Genet. 43, 441\u2013443 (2006).","journal-title":"J. Med. Genet."},{"key":"6384_CR10","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/nature13908","volume":"515","author":"I Iossifov","year":"2014","unstructured":"Iossifov, I. et al. The contribution of de novo coding mutations to autism spectrum disorder. 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