Nuzhat, Nafisa and Van Schil, Kristof and Liakopoulos, Sandra and Bauwens, Miriam and Rey, Alfredo Duenas and Kaeseberg, Stephan and Jaeger, Melanie and Willer, Jason R. and Winter, Jennifer and Truong, Hanh M. and Gruartmoner, Nuria and Van Heetvelde, Mattias and Wolf, Joachim and Merget, Robert and Grasshoff-Derr, Sabine and Van Dorpe, Jo and Hoorens, Anne and Stoehr, Heidi and Mansard, Luke and Roux, Anne-Francoise and Langmann, Thomas and Dannhausen, Katharina and Rosenkranz, David and Wissing, Karl M. and Van Lint, Michel and Rossmann, Heidi and Haeuser, Friederike and Nuernberg, Peter and Thiele, Holger and Zechner, Ulrich and Pearring, Jillian N. and De Baere, Elfride and Bolz, Hanno J. (2023) CEP162 deficiency causes human retinal degeneration and reveals a dual role in ciliogenesis and neurogenesis. JOURNAL OF CLINICAL INVESTIGATION, 133 (8): e161156. ISSN 0021-9738, 1558-8238
Full text not available from this repository. (Request a copy)Abstract
Defects in primary or motile cilia result in a variety of human pathologies, and retinal degeneration is frequently associated with these so-called ciliopathies. We found that homozygosity for a truncating variant in CEP162, a centrosome and microtubule-associated protein required for transition zone assembly during ciliogenesis and neuronal differentiation in the retina, caused late-onset retinitis pigmentosa in 2 unrelated families. The mutant CEP162-E646R*5 protein was expressed and properly localized to the mitotic spindle, but it was missing from the basal body in primary and photoreceptor cilia. This impaired recruitment of transition zone components to the basal body and corresponded to complete loss of CEP162 function at the ciliary compartment, reflected by delayed formation of dysmorphic cilia. In contrast, shRNA knockdown of Cep162 in the developing mouse retina increased cell death, which was rescued by expression of CEP162-E646R*5, indicating that the mutant retains its role for retinal neurogenesis. Human retinal degeneration thus resulted from specific loss of the ciliary function of CEP162.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEIN; ASSOCIATION; AXONEME; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Apr 2024 13:00 |
| Last Modified: | 18 Apr 2024 13:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60829 |
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