Global Aldh1a1 KO (Aldh1a1−/−) and knock-in (Aldh1a1C303A) strains.

The Aldh1a1−/−strain was developed and characterized by Fan et al. (1). Thesemice develop normally (1). The use of this strain has revealed important in vivo functions of ALDH1A1 in oxidizing retinal (1), regulating the metabolic response to a high-fat diet (2), and protecting against cataracts (3). In collaboration with the Gene Targeting Core at the University of Colorado Denver, our group generated an Aldh1a1C303A knock-in mouse line which carries a Cys>Ala point mutation at codon 303. This results in expression of intact ALDH1A1 proteins that are enzymatically-inactive (manuscript in preparation). In humans, genetic variants of ALDH1A1 (low enzyme activity) have been associated with increased alcohol sensitivity (4). Therefore, the Aldh1a1−/−and Aldh1a1C303A mouse strains represent useful animal models for investigating catalytic and/or non-catalytic functions of ALDH1A1 in the ethanol-induced pathophysiology. The Aldh1a1C303A strain is being backcrossed into the B6 background. 

References

  1. Fan X, Molotkov A, Manabe S, Donmoyer CM, Deltour L, Foglio MH, Cuenca AE, Blaner WS, Lipton SA, Duester G. (2003). Targeted disruption of Aldh1a1 (Raldh1) provides evidence for a complex mechanism of retinoic acid synthesis in the developing retina. Mol Cell Biol 23: 4637-48.

  2. Ziouzenkova O, Orasanu G, Sharlach M, Akiyama TE, Berger JP, Viereck J, Hamilton JA, Tang G, Dolnikowski GG, Vogel S, Duester G, Plutzky J. (2007). Retinaldehyde represses adipogenesis and diet-induced obesity. Nature Medicine 13: 695-702.

  3. 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.

  4. Eriksson CJ. (2001). The role of acetaldehyde in the actions of alcohol (update 2000). Alcohol Clin Exp Res 25: 15S-32S.