Alternative splicing in CEP290 mutant cats results in a milder phenotype than LCA CEP290 patients.

Autor: Minella AL; Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA., Narfström Wiechel K; Department of Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, Mssouri, USA., Petersen-Jones SM; Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Jazyk: angličtina
Zdroj: Veterinary ophthalmology [Vet Ophthalmol] 2023 Jan; Vol. 26 (1), pp. 4-11. Date of Electronic Publication: 2022 Dec 09.
DOI: 10.1111/vop.13052
Abstrakt: Purpose: The rdAc cat has an intronic mutation in the centrosomal 290 kDa (CEP290) gene resulting in a frameshift and a premature stop codon (c.6960 + 9 T > G, p.Ile2321AlafsTer3) predicted to truncate the protein by 157 amino acids. CEP290 mutations in human patients cause a range or phenotypes including syndromic conditions and severe childhood loss of vision while the rdAc cat has a milder phenotype. We sought to further characterize the effect of rdAc mutation on CEP290 expression.
Methods: TaqMan quantitative real-time polymerase chain reaction assays were used to compare wildtype and truncated transcript levels. Relative protein abundance was analyzed by Western blot. Immunohistochemistry (IHC) was performed to detect CEP290 protein.
Results: CEP290 mutant cats show low-level (17.4% of wildtype cats) use of the wildtype splice site and usage of the mutant splice site. Western analysis shows retina from cats homozygous for the mutation has CEP290 protein that likely comprises a combination of both wildtype and truncated protein. IHC detects CEP290 in affected and control retina labeling the region of the interconnecting cilium.
Conclusions: The comparably milder phenotype of CEP290 mutant cats is likely due to the retained production of some full-length CEP290 protein with possible functional contributions from presence of truncated protein.
(© 2022 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)
Databáze: MEDLINE
Externí odkaz: