Although the cell biology of haemopoietic stem cells (HSC) is relative
ly well understood, their molecular control is less well defined. Due
to the rarity of this cell type, their incompletely defined phenotype
and difficulty in generating null alleles by somatic transgenesis of H
SC, alternative approaches to their study have been sought. Embryonal
stem (ES) cells are toti-potential, can transmit transgenes through th
e germ line and have recently been shown to produce HSC in vitro. This
chapter reviews the utility of gene knock-outs in ES cells in the stu
dy of molecular haemopoiesis, indicates how ES cells can be used in vi
tro as a strategy both for the identification of genes controlling ear
ly haemopoietic events and the analysis of their function, and outline
s how emerging techniques that exploit the biology of ES cells might p
rove to be powerful tools in the genetic dissection of the mechanisms
controlling haemopoiesis.