Targeted Disruption of the flk2/flt3 Gene Leads to Deficiencies in Primitive Hematopoietic Progenitors

Immunity. 1995 Jul;3(1):147-61. doi: 10.1016/1074-7613(95)90167-1.

Abstract

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. However, they possessed specific deficiencies in primitive B lymphoid progenitors. Bone marrow transplantation experiments revealed a further deficiency in T cell and myeloid reconstitution by mutant stem cells. Mice deficient for both c-kit and flk2 exhibited a more severe phenotype characterized by large overall decreases in hematopoietic cell numbers, further reductions in the relative frequencies of lymphoid progenitors, and a postnatal lethality. Taken together, the data suggest that flk2 plays a role both in multipotent stem cells and in lymphoid differentiation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / physiology*
  • Base Sequence
  • Cell Differentiation
  • Gene Deletion
  • Hematopoiesis / physiology*
  • Hematopoietic Stem Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Proto-Oncogene Proteins / genetics*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • T-Lymphocytes / physiology*
  • fms-Like Tyrosine Kinase 3

Substances

  • Proto-Oncogene Proteins
  • Flt3 protein, mouse
  • Receptor Protein-Tyrosine Kinases
  • fms-Like Tyrosine Kinase 3