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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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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.
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