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.
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