TARGETED DISRUPTION OF THE FLK2 FLT3 GENE LEADS TO DEFICIENCIES IN PRIMITIVE HEMATOPOIETIC PROGENITORS/

The flk2 receptor tyrosine kinase has been implicated in hematopoietic development. Mice deficient in flk2 were generated. Mutants developed into healthy adults with normal mature hematopoietic populations. How ever, they possessed specific deficiencies in primitive B lymphoid pro genitors, Bone marrow transplantation experiments revealed a further d eficiency in T cell and myeloid reconstitution by mutant stem cells. M ice deficient for both c-kit and flk2 exhibited a more severe phenotyp e characterized by large overall decreases in hematopoietic cell numbe rs, further reductions in the relative frequencies of lymphoid progeni tors, and a postnatal lethality. Taken together, the data suggest that flk2 plays a role both in multipotent stem cells and in lymphoid diff erentiation.