April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Photoreceptor degeneration in the DHDDSK42E/K42E mouse
Author Affiliations & Notes
  • Yiwen Li
    Bascom Palmer Eye Institute, University of Miami, Miami, FL
  • Byron L Lam
    Bascom Palmer Eye Institute, University of Miami, Miami, FL
  • Ziqiang Guan
    Biochemistry, Duke University Medical Center, Durham, NC
  • Zhengying Wang
    Bascom Palmer Eye Institute, University of Miami, Miami, FL
  • Ning Wang
    Bascom Palmer Eye Institute, University of Miami, Miami, FL
  • Yihui Chen
    Bascom Palmer Eye Institute, University of Miami, Miami, FL
  • Rong Wen
    Bascom Palmer Eye Institute, University of Miami, Miami, FL
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4371. doi:
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      Yiwen Li, Byron L Lam, Ziqiang Guan, Zhengying Wang, Ning Wang, Yihui Chen, Rong Wen; Photoreceptor degeneration in the DHDDSK42E/K42E mouse. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4371.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Transgenic DHDDSK42E/K42E mice were created to reconstruct the genotype of a human mutation recently identified in the DHDDS mice gene encoding dehydrodolichol diphosphate synthase (DHDDS). This mutation changes a highly conserved Lys42 to Glu and is responsible for 12% of autosomal recessive RP (arRP) cases in patients of Ashkenazi Jewish (AJ) origin. The present work characterizes the retinal degeneration in the DHDDSK42E/K42E mice.

Methods: Transgenic mice with DHDDSK42E genotype were created by the knock-in (KI) technology and bred into homozygosity. Animals were kept in <50 lux 12:12 cyclic light. Eyes were collected from 3 month old animals, embedded in an Epon/Araldite mixture, and sectioned at 1 µm thickness to display the entire retina along the vertical meridian. Retinal sections were examined by light microscopy.

Results: The DHDDSK42E/K42E genotype was confirmed by PCR. A characteristic shortening of dolichol length distribution, similar to the shortening in patients, was found in plasma dolichols by liquid chromatography-mass spectrometry. In the 3 months DHDDSK42E/K42E mice, the outer segments (OS) of rod photoreceptors reduced to about half of the length seen in the age matched wild-type (wt) animals. In addition, the outer nuclear layer (ONL) thickness decreased to two-thirds compared to that of the wt controls.

Conclusions: The DHDDSK42E/K42E mice recapitulate the phenotype of retinal degeneration in patients and are a viable model of arRP caused by the K42E DHDDS mutation.

Keywords: 695 retinal degenerations: cell biology • 696 retinal degenerations: hereditary • 648 photoreceptors  
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