Accentuated response to phenylhydrazine and erythropoietin in mice genetically impaired for their GATA-1 expression (GATA-1(low) mice)

The response of mice genetically unable to up-regulate GATA-11 expression ( GATA-1(low) mice) to acute (phenylhydrazine [PHZ]-induced anemia) and chron ic (in vivo treatment for 5 days with 10 U erythropoietin (EPO) per mouse) erythroid stimuli was investigated. Adult GATA-1(low) mice are profoundly t hrombocytopenic (platelet counts [x 10(9)/L] 82.0 +/- 28.0 vs 840 +/- 170.0 of their control littermates, P<.001) but have a normal hermatocrit (Hot) (approximately .47 proportion of 1.0 [47%]). The spleens of these mutants a re 2.5-fold larger than normal and contain 5-fold more megakaryocytic (4A5( +)), erythroid (TER-119(+)), and bi potent (erythroid/megakaryocytic, TER-1 19(+)/4A5(+)) precursor cells. Both the marrow and the spleen of these anim als contain higher frequencies of burst-forming units-erythroid (BFU-E)- an d colony-forming units-erythroid (CFU-E)-derived colonies (2-fold and 6-fol d, respectively) than their normal littermates. The GATA-1(low) mice recove r 2 days faster from the PHZ-induced anemia than their normal littermates ( P<.01). In response to EPO, the Hot of the GATA-1(low) mice raised to .68 p roportion of 1.0 (68%) vs the .55 proportion of 1.0 (55%) reached by the co ntrols (P<.01). Both the GATA-1(low) and the normal mice respond to PHZ and EPO with similar (2- to 3-fold) increases in size and cellularity of the s pleen (increases are limited mostly to cells, both progenitor and precursor , of the erythroid lineage). However, in spite of the similar relative cell ular increases, the increases of all these cell populations are significant ly higher, In absolute cell numbers, in the mutant than in the wildtype mic e. In conclusion, the GATA-1(low) mutation increases the magnitude of the r esponse to erythroid stimuli as a consequence of the expansion of the eryth roid progenitor cells in their spleen. (Blood. 2001;97:3040-3050) (C) 2001 by The American Society of Hematology.