Mouse models in the study of the Ets family of transcription factors

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.