The Effect of Inactivating Heterozygous Mutation in NBS1 Gene on DNA Damage and Repair Markers and Apoptosis Markers in Mice

We studied the state of the DNA repair system and apoptosis in young mice carrying heterozygous inactivating mutation in theNBS1 gene (c.1971insT,p.Arg658Stop). In the peripheral blood cells of 4-month-oldNBS1insT males, the %DNA in the comet tail was higher by 10% than in wild-type mice (wt) (p<0.05). In hepatocytes ofNBS1insT mice, the proportion of γH2AX+ nuclear regions marking DNA double-strand breaks was lower by 2 times than in wt mice (p<0.05), which can be an indicator of less efficient DNA repair. In the kidney tissue ofNBS1insT mice, a tendency towards the proapoptotic ratio of Bax and Bcl-2 protein markers was revealed against the background of their reduced expression. Thus, the disturbances detectedNBS1insT mice in young age suggest that this model is promising for further studies of carcinogenesis.
Source: Bulletin of Experimental Biology and Medicine - Category: Biology Source Type: research