May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Development and Initial Characterization of the Aldh1a1(–/–)/Aldh3a1(–/–) Double Knockout Mice
Author Affiliations & Notes
  • N. Lassen
    Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, CO
  • W. Black
    Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, CO
  • D.W. Nees
    Laboratory of Molecular and Developmental Biology, National Eye Institute, Bethesda, MD
  • J. Piatigorsky
    Laboratory of Molecular and Developmental Biology, National Eye Institute, Bethesda, MD
  • G. Duester
    Developmental Biology Program, Burnham Institute, La Jolla, CA
  • V. Vasiliou
    Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, CO
  • Footnotes
    Commercial Relationships  N. Lassen, None; W. Black, None; D.W. Nees, None; J. Piatigorsky, None; G. Duester, None; V. Vasiliou, None.
  • Footnotes
    Support  NEI Grant 11490
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 3620. doi:
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      N. Lassen, W. Black, D.W. Nees, J. Piatigorsky, G. Duester, V. Vasiliou; Development and Initial Characterization of the Aldh1a1(–/–)/Aldh3a1(–/–) Double Knockout Mice . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3620.

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

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Abstract

Abstract: : Purpose: Mammalian cornea expresses ALDH3A1 and/or ALDH1A1 at high concentrations, whereas lens is characterized by the expression of mainly ALDH1A1. Aldh3a1 and Aldh1a1 transgenic single knockouts have no apparent developmental abnormalities. However, both mouse lines are prone to UVR–induced oxidative damage in the eye, thus supporting our hypothesis that these two proteins protect the ocular tissue against UVR–induced injury. To further investigate this hypothesis, we sought to generate and characterize an Aldh1a1/Aldh3a1 double knockout mouse line. Methods: Aldh1a1(–/–)/Aldh3a1(–/–) mice were generated by crossbreeding the Aldh1a1(–/–) and Aldh3a1(–/–) single knockouts. Corneal and lens transparency were evaluated in these mice by slit lamp microscopy. To characterize any compensation caused by the lack of both ALDHs in these mice, the expression of enzymes involved in 4–hydroxynonenal metabolism (alcohol dehydrogenase, aldose reductase and glutathione S–trasnferase), antioxidants (catalase and Cu–Zn superoxide dismutase), and other corneal crystallins (transketolase) was examined in the lens and the cornea by Western blot analysis. Results: The double–mutant mouse line was obtained in the F2 generation and the genotypes were examined by Southern blot and/or PCR analysis of genomic DNA. Aldh1a1/Aldh3a1–deficient mice were viable and fertile with no apparent corneal or lens abnormalities. The lack of ALDH1A1 or ALDH3A1 protein expression was confirmed by silver staining and immunoblot analyses. No compensation was observed in the expression of the 4–hydroxynonenal metabolizing enzymes or antioxidants in the cornea or lens of Aldh1a1(–/–)/Aldh3a1(–/–) mice. Conclusions: The double knockout mouse line described here provides a valuable animal model to study the combined roles of ALDH1A1 and ALDH3A1 in the physiology and pathophysiology of the eye.

Keywords: cornea: epithelium • genetics • transgenics/knock-outs 
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