Lucie Aumailley, Marie Julie Dubois, Tracy A Brennan, Chantal Garand, Eric R Paquet, Robert J Pignolo, André Marette, Michel Lebel
Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ-family DNA helicase (WRN). Mice lacking part of the helicase domain of the WRN ortholog exhibit several phenotypic features of WS. In this study, we generated a Wrn mutant line that, like humans, relies entirely on dietary sources of vitamin C (ascorbate) to survive, by crossing them to mice that lack the gulonolactone oxidase enzyme required for ascorbate synthesis. In the presence of 0.01% ascorbate (w/v) in drinking water, double-mutant mice exhibited a severe reduction in lifespan, small size, sterility, osteopenia, and metabolic profiles different from wild-type (WT) mice...
February 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology