AML1(- -) EMBRYOS DO NOT EXPRESS CERTAIN HEMATOPOIESIS-RELATED GENE TRANSCRIPTS INCLUDING THOSE OF THE PU.1 GENE/

The AML1 and PEBP2 beta/CBF beta genes encode the DNA-binding and non- binding subunits, respectively, of the heterodimeric transcription fac tor, PEBP2/CBF. Targeting each gene results in an almost identical phe notype, namely the complete lack of definitive hematopoiesis in the fe tal liver on embryonic day 11.5 (E11.5). We examined and compared the expression levels of various hematopoiesis-related genes in wild type embryos and in embryos mutated for AML1 or PEBP2 beta/CBF beta. The RN As were prepared from the yolk sacs of E9.5 embryos, from the aorta-go nad- mesonephros regions of E11.5 embryos and from the livers of E11.5 embryos and RT-PCR was performed to detect various gene transcripts. Transcripts were detected for most of the hematopoiesis-related genes that encode transcription factors, cytokines and cytokine receptors, e ven in tissues from homozygously targeted embryos. On the other hand, PU.1 transcripts were never detected in any tissue of AML1(-/-) or PEB P2 beta/CBF beta(-/-) embryos. In addition, transcripts for the Vav, f lk-2/flt-3, M-CSF receptor, G-CSF receptor and c-Myb genes were not de tected in certain tissues of the (-/-) embryos. The results suggest th at the expression of a particular set of hematopoiesis-related genes i s closely correlated with the PEBP2/CBF function.