The targeting vector was designed to insert a loxP site, a PGK-Puro selection cassette, a splice acceptor, an endogenous Dnmt3a exon 23 sequence, a polyA sequence, a STOP cassette (4xSV40pA), followed by a second loxP site into intron 22 upstream of a modified Dnmt3a exon 23 sequence containing the 2633G>A substitution that encodes an arginine-to-histidine mutation at amino acid 878 (R878H) commonly found in patients with aging-associated clonal hematopoiesis, acute myeloid leukemia (AML) and other haematological malignancies.