GSE112174
RNA-seq for MP, AML and MEFs from mice that carry a "knock-in" allele of the mutant splicing factor, U2af1(S34F), with or without homozygous deletion of the transcription factor, Runx1
We have generated mice that carry Cre-dependent "knock-in" alleles (MGS34F and IES34F) of U2af1(S34F), a mutation commonly encountered in human myelodysplastic syndromes and acute myeloid leukemia (AML). MEFs were generated from the progenies of these mice with those carrying a UBC-CreERT2 transgene, and were treated with 4-Hydroxytamoxifen (4OHT) to induce Cre-mediated recombination and subsequent U2af1(S34F) expression. Mice carrying the MGS34F allele were further crossed with those carrying a floxed Runx1 allele and Mx1-Cre. U2af1(S34F) expression and Runx1 deletion caused changes in gene expression and RNA splicing. Mice with a conditional "knock-in" U2af1(S34F) allele and conditional "knockout" alleles of Runx1 were mutagenized with low-dose N-Ethyl-N-Nitrosourea (ENU). Within 1.5 year, one of fourteen ENU-treated mice with U2af1(S34F) and Runx1 deletion developed AML, as did recipients of allografted splenic cells from two other such mice, but AML did not arise from cells with other genotypes or mice without ENU treatment. Overall design: mRNA sequencing for MEFs, MPs, and AML samples of the indicated genotypes in mice