tie2creinduced inactivation of a conditional mutant nf1 allele in mouse results in a myeloproliferative disorder that models juvenile myelomonocytic leukemia neurofibromatosis type one nf1 is a common genetic disorder affecting 14000 births and is characterized by benign and malignant tumors children with nf1 are predisposed to juvenile myelomonocytic leukemia the nf1 gene encodes neurofibromin which can function as a ras gtpaseactivating protein neurofibromin deficiency in mice leads to midgestation lethality due to cardiovascular defects we have previously shown that conditional inactivation of nf1 using tie2cre recapitulates the heart defects seen in nf1 embryos tie2cre transgenic mice express cre recombinase in all endothelial cells here we show that tie2cremediated deletion of nf1 also leads to excision of nf1 in the hematopoietic lineage surviving mice exhibit a myeloproliferative disorder similar to juvenile myelomonocytic leukemia seen in nf1 patients these mice provide a useful model to study neurofibromin deficiency in hematopoiesis furthermore defects in tie2creexpressing progenitors that result in heart and blood defects suggest that related heart and blood disorders in nf1 and other syndromes represent disorders of the hemangioblast