PU.1 exhibits partial functional redundancy with Spi-B, but not with Ets-1 or Elf-1

Previously it was shown that the Ets proteins, PU.1 and Spi-B, exhibit functional redundancy in B lymphocytes. To investigate the possibility that PU.1 or Spi-B or both share overlapping roles with Ets-1 or Elf-1, PU.1^+/-Ets-1^-/-, PU.1^+/-Elf-1^-/-, and Spi-B^-/-ETS-1^-/- animals were generated. No blood cell defects were observed in these animals except those previously reported for Ets-1^-/- mice. Therefore, no genetic overlap was detected between PU.1 or Spi-B with Ets-1 or Elf-1. In contrast, the results confirmed functional redundancy for PU.1 and Spi-B in that PU.1^+/-Spi-B^-/- bone marrow progenitors yielded smaller colonies in methylcellulose cultures than did wild-type, PU.1^+/- or Spi- B^-/- progenitors. In addition, PU.1^+/-Spi- B^+/+, PU.1^+/-Spi-B^+/-, and PU.1^+/- Spi-B^-/- mice displayed extramedullary splenic hematopoiesis. In summary, PU.1 and Spi-B regulate common target genes required for proliferation of hematopoietic progenitors or their committed descendants, whereas Ets-1 or Elf-1 do not appear to regulate shared target genes with PU.1 or Spi-B.