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Image Search Results
Journal: Advanced Science
Article Title: KMT2D Deficiency Promotes Myeloid Leukemias which Is Vulnerable to Ribosome Biogenesis Inhibition
doi: 10.1002/advs.202206098
Figure Lengend Snippet: Kmt2d mutation by CRISPR/Cas9 promotes AML in mice. A) Schematic experimental design for mouse modeling using CRISPR/Cas9 system. Trp53 −/− ; Cas9 mouse HSPCs were transduced with mCherry‐linked sg Kmt2d ‐sg Nf1 ‐sg Cas9 or sgScramble‐sg Nf1 ‐sg Cas9 , and then transplanted into sub‐lethally irradiated syngeneic mice. B) Kaplan–Meier survival curves of mice transplanted with Trp53 −/− ; Cas9 HSPCs transduced with sgScramble‐sg Nf1 ‐sg Cas9 (blue; n = 5), sg Kmt2d_ #1‐sg Nf1 ‐sg Cas9 (red, n = 5), or sg Kmt2d_# 2‐sg Nf1 ‐sg Cas9 (orange; n = 5). ** p < 0.01 (log‐rank test). C) WBC, Hb, and PLT counts of sgScramble and sg Kmt2d mice 2 months post‐transplant. Graph represents the mean ± SD; ** p < 0.01, *** p < 0.001, ns, not significant (unpaired two‐tailed t ‐test). D) Representative flow cytometric profiles showing the expression of CD11b/Gr‐1, B220/CD3ε and c‐Kit in bone marrow cells of sacrificed TNKC ( Trp53 −/− ; sg Nf1 ; sg Kmt2d; sg Cas9 ) mice. E) Representative images of histological analyses of blood, spleen, liver, and bone marrow of sacrificed TNKC mice. F) T7 endonuclease I assay on Kmt2d in bone marrow cells of sacrificed TNKC mice. G) Mutation analyses of the Kmt2d regions targeted by CRISPR/Cas9 of TNKC bone marrow cells. Representative Sanger sequences of single TA clones.
Article Snippet: sgRNAs were designed by the ATUM
Techniques: Mutagenesis, CRISPR, Transduction, Irradiation, Two Tailed Test, Expressing, T7EI Assay, Clone Assay