AKR1B8 kncokout mouse model Exome sequence analysis. Mus musculus strain:C57BL/6 Mouse Strain

Etiopathological factors of ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC) remain unclear. Aldo-keto reductase 1B10 (AKR1B10), a carbonyl detoxicant and fatty acid/lipid synthesis regulator, is primarily expressed in colon, but lost or remarkably decreased in over 90% of UC and CAC tissues. Targeted disruption of aldo-keto reductase 1B8 (AKR1B8), an orthologue of human AKR1B10 in mice, disturbed the self-renewal and injury repair of colonic cryptic cells due to a decrease in lipid synthesis from butyrate. AKR1B8 deficient mice are highly susceptible to colitis induced by dextran sulfate sodium (2%) and to carbonyl and oxidative DNA damage, leading to colitis-associated tumorigenesis. Therefore, AKR1B8 is a critical protein that affects the dynamic homeostasis of self-renewal and barrier function of colonic epithelium.