June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
A Mouse Model of Schnyder Corneal Dystrophy with the N100S Point Mutation
Author Affiliations & Notes
  • Fei Dong
    Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States
  • Xueting Jin
    Laboratory of Experimental Atherosclerosis, NIH, Bethesda, Maryland, United States
  • Michelle Boettler
    Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States
  • Sciulli Harrison
    Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States
  • Mones S Abu-Asab
    Histopathology Core Facility, NIH/NEI, Bethesda, Maryland, United States
  • Shurong Wang
    Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States
    Ophthalmology, the Second Hospital of Jilin University, Changchun, Jilin, China
  • Yueh-Chiang Hu
    Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Maria M Campos
    Histopathology Core Facility, NIH/NEI, Bethesda, Maryland, United States
  • Howard S Kruth
    Laboratory of Experimental Atherosclerosis, NIH, Bethesda, Maryland, United States
  • Jayne S Weiss
    Department of Ophthalmology, Pathology and Pharmacology, Louisiana State University, New Orleans, Louisiana, United States
  • Winston W Y Kao
    Ophthalmology, University of Cincinnati, Cincinnati, Ohio, United States
  • Footnotes
    Commercial Relationships   Fei Dong, None; Xueting Jin, None; Michelle Boettler, None; Sciulli Harrison, None; Mones Abu-Asab, None; Shurong Wang, None; Yueh-Chiang Hu, None; Maria Campos, None; Howard Kruth, None; Jayne Weiss, None; Winston Kao, None
  • Footnotes
    Support  NIH/NEI grants RO1 EY011845, R01 021768, unrestricted Departmental grant of Research to Prevent Blindness and Ohio Eye Research Foundation
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3427. doi:
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    • Get Citation

      Fei Dong, Xueting Jin, Michelle Boettler, Sciulli Harrison, Mones S Abu-Asab, Shurong Wang, Yueh-Chiang Hu, Maria M Campos, Howard S Kruth, Jayne S Weiss, Winston W Y Kao; A Mouse Model of Schnyder Corneal Dystrophy with the N100S Point Mutation. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3427.

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

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Abstract

Purpose : Schnyder corneal dystrophy (SCD) is an autosomal dominant disease in humans, which is caused by mutations in the Ubia prenyltransferase domain containing 1 (UBIAD1) gene in chromosome 1 p36 and is characterized by progressive corneal opacification resulting from abnormal deposition of cholesterol and phospholipids. To investigate the pathogenesis and develop therapeutic regimens for SCD, we generated a mutant mouse line carrying a N100S mutation in Ubiad1, which mimics human N102S mutation.

Methods : The Ubiad1N100S mouse line was generated by the CRISPR/Cas9 genome editing technique. Twenty corneas from ten individual mice of the genotypes Ubiad1N100S/N100S, Ubiad1N100/WT and wild type (WT) lines were subjected to in vivo confocal microscopy (Heidelberg Retinal Tomograph-HRTII Rostock Cornea Module) at the age of 6 weeks. Quantitative analysis of deposits based on in vivo confocal microscopic images was conducted using Image J software. Filipin staining was performed on cryosections of Ubiad1N100S/N100S, Ubiad1N100S/WT and WT mice to determine the cholesterol deposition in cornea. Ubiad1N100S/N100S, Ubiad1N100S/WT and WT mice corneas were examined with electron microscopy.

Results : The Ubiad1N100S point mutation mouse line has been successfully created using the CRISPR/Cas9 technique. Homozygous Ubiad1N100S/N100S and heterozygous Ubiad1N100S/WT mice are fertile and do not manifest apparent pathology except for anterior corneal. Filipin staining demonstrated elevated cholesterol in cornea of Ubiad1N100S/N100S and Ubiad1N100S/WT Electron microscopy revealed mitochondrial degeneration in the epithelium and keratocytes. These observations implied that the pathogenesis of SCD might be related to cholesterol accumulation and mitochondrial regulation of lipid metabolism.

Conclusions : The Ubiad1N100S mouse provides a promising animal model of SCD which may facilitate understanding SCD pathogenesis and development of therapeutic regimens for SCD.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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