Figure 1. IDH2R140Q–t Mice Demonstrate Extramedullary Hematopoiesis Characterized by Spleen Enlargement and Expansion of Hematopoietic Stem/Progenitor Cells.
(A) Schematic depicting the strategy for generation of an inducible IDH2R140Q allele in the mouse. Following Flp-mediated recombination, the IDH2R140Q cDNA flanked by a tetracycline response element (TRE) and a protamine-1 poly-A cassette is integrated into the ColA1 locus. The PGK promoter drives hygromycin resistance, allowing selection of integrants.
(B) 2-HG in BM MNCs measured by LC-MS following 8 weeks of transgene induction.
(C) Representative flow cytometry analysis of bone marrow mononuclear cells and splenocytes from mice treated with doxycycline for 8 weeks or 7 months. Numbers indicate cells within the gate as a percentage of all living cells in the sample.
(D) Spleen weights of mice following 8 weeks of doxycycline treatment.
(E) Percentage of cKit+Sca1+Lin− (KSL) cells in the spleens of mice following 8 weeks of doxycycline treatment.
(F) Percentage of KSL cells in the bone marrow of mice following 7 months of doxycycline treatment.
(G) Percentage of CD48−CD150+KSL hematopoietic stem cells in the bone marrow of mice following 7 months of doxycycline treatment.
Error bars, mean ± SEM; p value calculated using a two-tailed unpaired Student’s t test. See also Figure S1.