The usherin mutation c.2299delG leads to its mislocalization and disrupts interactions with whirlin and VLGR1

Lars Tebbe, Maggie L. Mwoyosvi, Ryan Crane, Mustafa S. Makia, Mashal Kakakhel, Dominic Cosgrove, Muayyad R. Al-Ubaidi () and Muna I. Naash ()
Additional contact information
Lars Tebbe: University of Houston
Maggie L. Mwoyosvi: University of Houston
Ryan Crane: University of Houston
Mustafa S. Makia: University of Houston
Mashal Kakakhel: University of Houston
Dominic Cosgrove: Boys Town National Research Hospital
Muayyad R. Al-Ubaidi: University of Houston
Muna I. Naash: University of Houston

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: Abstract Usher syndrome (USH) is the leading cause of combined deafness-blindness with type 2 A (USH2A) being the most common form. Knockout models of USH proteins, like the Ush2a-/- model that develops a late-onset retinal phenotype, failed to mimic the retinal phenotype observed in patients. Since patient’s mutations result in the expression of a mutant protein and to determine the mechanism of USH2A, we generated and evaluated an usherin (USH2A) knock-in mouse expressing the common human disease-mutation, c.2299delG. This mouse exhibits retinal degeneration and expresses a truncated, glycosylated protein which is mislocalized to the photoreceptor inner segment. The degeneration is associated with a decline in retinal function, structural abnormalities in connecting cilium and outer segment and mislocaliztion of the usherin interactors very long G-protein receptor 1 and whirlin. The onset of symptoms is significantly earlier compared to Ush2a-/-, proving expression of mutated protein is required to recapitulate the patients’ retinal phenotype.

Date: 2023
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-36431-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36431-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-36431-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().