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-8 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. (Blood, 2001; 97:2908-2912) (C) 2001 by The American Society of Hematology.