Tie2-Cre-Induced Inactivation of a Conditional Mutant Nf1 Allele in Mouse Results in a Myeloproliferative Disorder that Models Juvenile Myelomonocytic Leukemia

Academic Article


  • Neurofibromatosis type one (NF1) is a common genetic disorder affecting 1:4000 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 GTPase-activating protein. Neurofibromin deficiency in mice leads to mid-gestation lethality due to cardiovascular defects. We have previously shown that conditional inactivation of Nf1 using Tie2-Cre recapitulates the heart defects seen in Nf1-/- embryos. Tie2-Cre transgenic mice express Cre recombinase in all endothelial cells. Here, we show that Tie2-Cre-mediated 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 Tie2-Cre-expressing 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.
  • Authors

    Published In

  • Pediatric Research  Journal
  • Digital Object Identifier (doi)

    Author List

  • Gitler AD; Kong Y; Choi JK; Zhu Y; Pear WS; Epstein JA
  • Start Page

  • 581
  • End Page

  • 584
  • Volume

  • 55
  • Issue

  • 4