bioRxivPathologyPreprint
Clonal hematopoiesis driven by Dnmt3a mutations promotes metabolic disease development
Bowen YaniD, Qingchen YuaniD, Prabhjot KauriD, Annalisse R. McKee, Daniil E. ShabashviliiD, Olga A. GuryanovaiD
Abstract
Clonal hematopoiesis (CH) is associated with an increased risk of non-hematologic chronic diseases including metabolic disorders, yet the causality remains poorly defined. DNMT3A is the most frequently altered gene in CH, commonly through monoallelic loss-of-function (LOF) and Arg882His (RH) hotspot mutations. Here we demonstrate in a mouse model that CH driven by Dnmt3a RH and especially LOF promotes obesity, diabetes, and chronic liver disease, further exacerbated by high-fat diet (HFD).
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