Global Aldh3a1 KO (Aldh3a1−/−) and knock-in (Aldh3a1C244A) strains

The Aldh3a1−/− strain was developed by Piatigorsky’s lab at NEI in a 129sv background (1). Using these and our Aldh3a1−/− congenic mice, we have demonstrated an essential role for ALDH3A1 in protecting against cataract formation (2) and corneal hazing (3). Recently, ALDH3A1 was reported to participate in ethanol/ACA metabolism (4). In collaboration with the Yale Genome Editing Center at the Yale School of Medicine, we have generated an Aldh3a1 knock-in mouse strain using the CRISPR-associated protein (Cas) gene editing technology. In a similar manner as the Aldh1a1 knock-in strain, the Aldh3a1C244A mutant mice express stable but enzymatically-inactive ALDH3A1 protein due to the Cys>Ala mutation at the codon 244 (5). Both Aldh3a1−/− and Aldh3a1C244A mice are fertile and display no overt phenotype.

1. Nees DW, Wawrousek EF, Robison WG, Jr., Piatigorsky J. (2002). Structurally normal corneas in aldehyde dehydrogenase 3a1-deficient mice. Mol Cell Biol 22: 849-55.
   
2. Lassen N, Bateman JB, Estey T, Kuszak JR, Nees DW, Piatigorsky J, Duester G, Day BJ, Huang J, Hines LM, Vasiliou V. (2007). Multiple and additive functions of ALDH3A1 and ALDH1A1: cataract phenotype and ocular oxidative damage in Aldh3a1(-/-)/Aldh1a1(-/-) knock-out mice. J Biol Chem 282: 25668-76.
   
3. Chen Y, Jester JV, Anderson DM, Marchitti SA, Schey KL, Thompson DC, Vasiliou V. (2016). Corneal haze phenotype in Aldh3a1-null mice: In vivo confocal microscopy and tissue imaging mass spectrometry. Chem Biol Interact
   
4. Chen CH, Cruz LA, Mochly-Rosen D. (2015). Pharmacological recruitment of aldehyde dehydrogenase 3A1 (ALDH3A1) to assist ALDH2 in acetaldehyde and ethanol metabolism in vivo. Proc Natl Acad Sci U S A 112: 3074-9.
   
5. Koppaka V, Chen Y, Mehta G, Orlicky DJ, Thompson DC, Jester JV, Vasiliou V. (2016). ALDH3A1 Plays a Functional Role in Maintenance of Corneal Epithelial Homeostasis. PLoS One 11: e0146433.