GATA factor transgenes under GATA-1 locus control rescue germline GATA-1 mutant deficiencies

GATA-1 germline mutation in mice results in embryonic lethality due to defe ctive erythroid cell maturation, and thus other hematopoietic GATA factors do not compensate for the loss of GATA-1, To determine whether the obligate presence of GATA-1 in erythroid cells is due to its distinct biochemical p roperties or spatiotemporal patterning, we attempted to rescue GATA-1 mutan t mice with hematopoietic GATA factor complementary DNAs (cDNAs) placed und er the transcriptional control of the GATA-1 gene. We found that transgenic expression of a GATA-1 cDNA fully abrogated the GATA-1-deficient phenotype , Surprisingly, GATA-2 end GATA-3 factors expressed from the same regulator y cassette also rescued the embryonic lethal phenotype of the GATA-1 mutati on. However, adult mice rescued with the latter transgenes developed anemia , while GATA-1 transgenic mice did not. These results demonstrate that the transcriptional control dictating proper GATA-1 accumulation is the most cr itical determinant of GATA-1 activity during erythropoiesis, The results al so show that there are biochemical distinctions among the hematopoietic GAT A proteins and that during adult hematopoiesis the hematopoietic GATA facto rs are not functionally equivalent. (C) 2000 by The American Society of Hem atology.