Submitted January 31, 2006
Accepted May 8, 2006
Somatic activation of a conditional
KrasG12D allele causes ineffective
erythropoiesis in vivo
Benjamin S Braun, Joehleen A Archard, Jessica A Van Ziffle, David A Tuveson, Tyler E Jacks, and Kevin Shannon*
Department of Pediatrics, University of California, San Francisco, CA, USA
Department of Medicine, University of Pennsylvania, PA, USA
Department of Biology, Massachusetts Institute of Technology, MA, USA
* Corresponding author; email: kevins{at}itsa.ucsf.edu.
Somatic activation of a conditional targeted
KrasG12D allele induces a fatal
myeloproliferative disease in mice that closely models
juvenile and chronic myelomonocytic leukemia. These mice
consistently develop severe and progressive anemia
despite adequate numbers of clonogenic erythroid
progenitors in the bone marrow and expanded splenic
hematopoiesis. Ineffective erythropoiesis is
characterized by impaired differentiation. These results
demonstrate that endogenous levels of oncogenic Ras have
cell-lineage specific effects, and support efforts to
modulate Ras signaling for therapy of anemia in patients
with myelodysplastic syndromes and myeloproliferative
disorders.
