June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
An inducible transgenic mouse model of TGFBI-related corneal stromal dystrophy
Author Affiliations & Notes
  • Andrew Huang
    Ophthalmology & Visual Sciences, Washington Univ School of Med, St Louis, MO
  • Chia-Yang Liu
    Ophthalmology, University of Cincinnati, Cincinnati, OH
  • Yujin Zhang
    Ophthalmology, University of Cincinnati, Cincinnati, OH
  • Hongshan Liu
    Ophthalmology, University of Cincinnati, Cincinnati, OH
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 4739. doi:
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      Andrew Huang, Chia-Yang Liu, Yujin Zhang, Hongshan Liu; An inducible transgenic mouse model of TGFBI-related corneal stromal dystrophy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4739.

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

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Abstract

Purpose: Mutations of transforming growth factor-beta inducible protein (TGFBI) have been associated with various corneal epithelial or stromal dystrophies. The pathogenic implications of mutant TGFBI for these dystrophies have been elusive, partially due to the lack of animal models specific for TGFBI-related corneal dystrophy. Herein, we report a doxycycline-inducible transgenic mouse model of corneal stromal dystrophy caused by R124H mutation of TGFBI, which is associated with granular corneal dystrophy II (GCD 2) or Avellino corneal dystrophy (ACD).

Methods: Human TGFBI cDNA with R124H mutation was used to make the transgenic mouse line (TRE-TGFBIR124H). The functional TRE-TGFBIR124H lines were crossed with K14rtTA to create bi-transgenic mice, K14rtTA/TRE-TGFBIR124H (K14/TGFBIR124H), in which TGFBIR124H was expressed in K14+ cells by feeding the pregnant mice with doxycycline-containing chow right after mating (E0). HRT-II in vivo microscopy was used to scan mouse corneas for 3D reconstruction of the TGFBIR124H corneal deposits. RT-PCR and Western blots were performed to analyze TGFBIR124H expression.

Results: RT-PCR and Western blots confirmed the expression of TGFBIR124H in the doxycycline-fed bi-transgenic mice. Corneal opacities were noticed in the K14/TGFBIR124H mice on postnatal day 42 and not in the TRE-TGFBIR124H single transgenic littermates. Serial HRT-II scannings confirmed the presence of progressive stromal opacity as well as multiple protein aggregates in the cornea of K14/TGFBIR124H mice.

Conclusions: We have generated an inducible transgenic mouse model of TGFBIR124H-related corneal stromal dystrophy. Its clinical phenotype is in resemblance of GCD 2. Such a mouse model may provide better insight to the pathogenesis of TGFBI-related corneal dystrophies.

Keywords: 482 cornea: epithelium • 637 pathology: experimental • 660 proteins encoded by disease genes  
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