# Pathological and functional consequences of dimerization-deficient rhodopsin mutations

> **NIH NIH F32** · DUKE UNIVERSITY · 2020 · $65,310

## Abstract

PROJECT SUMMARY/ABSTRACT
The overall goal of this proposal is to bridge two major unsolved problems in basic and translational vision
research: the functional role of rhodopsin dimerization and the pathophysiological mechanisms of retinitis
pigmentosa, an inherited degenerative disease of the retina. Many mutations that cause retinitis pigmentosa
are in the gene encoding the G protein-coupled receptor (GPCR) rhodopsin. Recent work has shown that three
rhodopsin mutations, including F45L and F220C considered in this application, fail to dimerize in vitro. The
central hypothesis of this proposal is that the inability of the F45L and F220C mutants to dimerize impedes
normal photoreceptor function, ultimately leading to photoreceptor degeneration. This hypothesis will be tested
using knock-in mouse models bearing either the F45L or the F220C rhodopsin mutation. Three Specific Aims
are proposed. First, we will quantitatively describe the extent and time course of photoreceptor degeneration in
each mouse, analyze photoreceptor ultrastructure, and examine rhodopsin trafficking. Second, we will analyze
the status of rhodopsin dimerization in the native photoreceptor membranes of these mice. Third, we will
investigate the ability of these mutants to support phototransduction through a combination of biochemical and
electrophysiological approaches. Taken together, the proposed studies are likely to contribute to our basic
understanding of the role that receptor dimerization plays in GPCR signaling and the pathophysiological
mechanisms underlying visual loss in congenital blinding diseases.

## Key facts

- **NIH application ID:** 9872022
- **Project number:** 5F32EY029929-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Tylor Robert Lewis
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872022

## Citation

> US National Institutes of Health, RePORTER application 9872022, Pathological and functional consequences of dimerization-deficient rhodopsin mutations (5F32EY029929-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9872022. Licensed CC0.

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