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

Author

Listed:
  • Lars Tebbe

    (University of Houston)

  • Maggie L. Mwoyosvi

    (University of Houston
    University of Oklahoma Health Sciences Center)

  • 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)

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.

Suggested Citation

  • Lars Tebbe & Maggie L. Mwoyosvi & Ryan Crane & Mustafa S. Makia & Mashal Kakakhel & Dominic Cosgrove & Muayyad R. Al-Ubaidi & Muna I. Naash, 2023. "The usherin mutation c.2299delG leads to its mislocalization and disrupts interactions with whirlin and VLGR1," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36431-1
    DOI: 10.1038/s41467-023-36431-1
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