To elucidate the functional impact of CH with DNMT3A LOF and RH mutations on metabolic disease development, we created a mouse bone marrow transplantation–based chimeric model with 20% of Dnmt3a+/– (representing LOF), Dnmt3a+/R878H (corresponding to human RH), or WT control cells (marked by pan-leukocytic CD45.2) mixed with 80% WT support (CD45.1) to mimic a clinically meaningful large CH clone (Figure 1B and Supplemental Figure 1, A and B; supplemental material available online with this article; https://doi.org/10.1172/JCI197100DS1). This evidence concerns the gene DNMT3A and metabolic disease.