# Characterization of DHDDS RP59 Knockin Models of Retinitis Pigmentosa

> **NIH NIH F31** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2022 · $38,552

## Abstract

Project Summary/Abstract
Retinitis pigmentosa (RP) is a heterogeneous group of disorders that cause retinal degeneration. To date,
mutations in more than 58 genes have been linked to classic retinitis pigmentosa, and collectively all forms of
inherited retinal dystrophies involves at least 300 genes. My studies are focused on retinitis pigmentosa-59
(RP59), a non-syndromic autosomal recessive form of RP caused by mutations in the dehydrodolichyl
diphosphate synthase (DHDDS) gene, localized to exon 3 on chromosome 1p36.11. The most prevalent
mutation is K42E, while T206A and R98W also have been reported. We generated a murine Dhdds K42E knock-
in mouse model using CRISPR/Cas9 gene editing technology. Preliminary data shows significant reduction of
ERG b-wave amplitudes and we have reported marked GFAP up-regulation, without retinal degeneration or
decreased protein N-glycosylation. This suggests that defective DHDDS-dependent retinal degeneration may be
more complicated than simply a loss-of-function mechanism due to altered protein glycosylation. To better
understand the basis for selective retinal pathology associated with RP59 mutations, we plan to characterize the
DhddsK42E/K42E knock-in mouse anatomically and physiologically. Additionally, we will create and analyze two new
models of DHDDS-related inherited retinal disease, Dhdds T206A/T206A and DhddsT206A/K42E. Studying the retina in
these mouse models will give us insight into the pathophysiology of this inherited disorder, and may lead to novel
treatment options for this disorder.

## Key facts

- **NIH application ID:** 10507785
- **Project number:** 5F31EY032764-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Mai N Nguyen
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $38,552
- **Award type:** 5
- **Project period:** 2021-03-15 → 2026-03-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10507785

## Citation

> US National Institutes of Health, RePORTER application 10507785, Characterization of DHDDS RP59 Knockin Models of Retinitis Pigmentosa (5F31EY032764-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10507785. Licensed CC0.

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