biostudies-literatureDowdy CRNIA NIH HHSNCI NIH HHS1048-57https://www.ebi.ac.uk/biostudies/studies/S-EPMC2830828biostudies-literatureUnknown19(6)Runx1 is a key hematopoietic transcription factor required for definitive hematopoiesis and is a frequent target of leukemia-related chromosomal translocations. The resulting fusion proteins, while retaining DNA binding activity, display loss of subnuclear targeting and associated transactivation functions encoded by the C-terminus of the protein. To define the precise contribution of the Runx1 C-terminus in development and leukemia, we created a knock-in mouse with a C-terminal truncation by introducing a single nucleic acid substitution in the native Runx1 locus. This mutation (Runx1(Q307X)) models genetic lesions observed in patients with leukemia and myeloproliferative disorders. The Runx1(Q307X) homozygous mouse exhibits embryonic lethality at E12.5 due to central nervous system hemorHuman molecular geneticsDefinitive hematopoiesis requires Runx1 C-terminal-mediated subnuclear targeting and transactivation.PMC2830828P01 CA082834R01 AG030228Lian JBDowdy CRVradii DJones SNStein GSXie RLi XStein JLZaidi SKHussain SFrederick Dvan Wijnen AJJaved AfalseDefinitive hematopoiesis requires Runx1 C-terminal-mediated subnuclear targeting and transactivation.Runx1 is a key hematopoietic transcription factor required for definitive hematopoiesis and is a frequent target of leukemia-related chromosomal translocations. The resulting fusion proteins, while retaining DNA binding activity, display loss of subnuclear targeting and associated transactivation functions encoded by the C-terminus of the protein. To define the precise contribution of the Runx1 C-terminus in development and leukemia, we created a knock-in mouse with a C-terminal truncation by introducing a single nucleic acid substitution in the native Runx1 locus. This mutation (Runx1(Q307X)) models genetic lesions observed in patients with leukemia and myeloproliferative disorders. The Runx1(Q307X) homozygous mouse exhibits embryonic lethality at E12.5 due to central nervous system hemor2010-01-01T00:00:00Z2010 Mar2025-04-21T18:43:22.822Z2019-03-27T00:28:59ZS-EPMC28308282003501210.1093/hmg/ddp568