The Ets family of transcription factors is one of a growing number of maste
r regulators of development. This family was originally defined by the pres
ence of a conserved DNA binding domain, the Ets domain. To date, nearly 30
members of this family have been identified and implicated in a wide range
of physiological and pathological processes. Despite the likely importance
of Ets-family members, each of their precise roles has not been delineated.
Herein, we describe the elucidation of essential functions of a few of the
se family members in vivo using knockout mouse models, Of the knockouts gen
erated to date, the majority shows important functions in hematopoiesis, ra
nging from PU.1, a principle regulator of myelo-lymphopoiesis, to Spi-B whi
ch regulates the proper function of terminally differentiated cells. Ets1 w
as shown to be of intermediate importance as a regulator of pan-lymphoid de
velopment. Other Ets family members such as Fli1 and TEL1 display distinct
and/or overlapping functions in vasculo/angiogenesis, hemostasis and hemato
poiesis. The remaining knockouts generated, Ets2 and Er81, show non-hematop
oietic defects related to extraembryonic development and neurogenesis, resp
ectively. The pioneering group of knockout models described reveals only th
e most distinct functions of each of these Ets family members. A better und
erstanding of the roles and hierarchies of Ets family members in cellular d
ifferentiation will come with the generation of new null alleles in previou
sly untargeted family members, more mutant alleles in members already disru
pted, double knockouts, ES cell differentiation and chimera rescue experime
nts, and tissue-specific inducible knockouts.