A Functional C-Myb Gene Is Required for Normal Murine Fetal Hepatic Hematopoiesis

Cell. 1991 May 17;65(4):677-89. doi: 10.1016/0092-8674(91)90099-k.

Abstract

The c-myb proto-oncogene encodes a sequence-specific DNA-binding protein. To better understand its normal biological function, we have altered the c-myb gene by homologous recombination in mouse embryonic stem cells. Resulting homozygous c-myb mutant mice displayed an interesting phenotype. At day 13 of gestation these mice appeared normal, suggesting that c-myb is not essential for early development. By day 15, however, the mutant mice were severely anemic. Analysis indicated that embryonic erythropoiesis, which occurs in the yolk sac, was not impaired by the c-myb alteration. Adult-type erythropoiesis, which first takes place in the fetal liver, was greatly diminished in c-myb mutants, however. Additional hematopoietic lineages were similarly affected. These results are compatible with a role for c-myb in maintaining the proliferative state of hematopoietic progenitor cells.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Southern
  • Cell Line
  • Chimera
  • DNA / genetics
  • DNA / isolation & purification
  • DNA-Binding Proteins / genetics*
  • Erythropoiesis
  • Fetus
  • Globins / genetics
  • Hematopoiesis*
  • Heterozygote
  • Homozygote
  • Liver / embryology
  • Liver / physiology*
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Oligonucleotide Probes
  • Phenotype
  • Polymerase Chain Reaction / methods
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-myb
  • Proto-Oncogenes*
  • RNA / genetics
  • RNA / isolation & purification
  • Restriction Mapping

Substances

  • DNA-Binding Proteins
  • Oligonucleotide Probes
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-myb
  • RNA
  • Globins
  • DNA
  • Protein-Tyrosine Kinases