title: Accentuated response to phenylhydrazine and erythropoietin in mice genetically impaired for their GATA-1 expression (GATA-1(low) mice).
abstract: The response of mice genetically unable to up-regulate GATA-1 expression (GATA-1(low) mice) to acute (phenylhydrazine [PHZ]-induced anemia) and chronic (in vivo treatment for 5 days with 10 U erythropoietin [EPO] per mouse) erythroid stimuli was investigated. Adult GATA-1(low) mice are profoundly thrombocytopenic (platelet counts [x 10(9)/L] 82.0 +/- 28.0 vs 840 +/- 170.0 of their control littermates, P <.001) but have a normal hematocrit (Hct) (approximately.47 proportion of 1.0 [47%]). The spleens of these mutants are 2.5-fold larger than normal and contain 5-fold more megakaryocytic (4A5(+)), erythroid (TER-119(+)), and bipotent (erythroid/megakaryocytic, TER-119(+)/4A5(+)) precursor cells. Both the marrow and the spleen of these animals contain higher frequencies of burst-forming units-erythroid (BFU-E)- and colony-forming units-erythroid (CFU-E)-derived colonies (2-fold and 6-fold, respectively) than their normal littermates. The GATA-1(low) mice recover 2 days faster from the PHZ-induced anemia than their normal littermates (P <.01). In response to EPO, the Hct of the GATA-1(low) mice raised to.68 proportion of 1.0 (68%) vs the.55 proportion of 1.0 (55%) reached by the controls (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 spleen (increases are limited mostly to cells, both progenitor and precursor, of the erythroid lineage). However, in spite of the similar relative cellular increases, the increases of all these cell populations are significantly higher, in absolute cell numbers, in the mutant than in the wild-type mice. In conclusion, the GATA-1(low) mutation increases the magnitude of the response to erythroid stimuli as a consequence of the expansion of the erythroid progenitor cells in their spleen.
authors.affiliation: Department of Hematology and Istituto di Oncologia and Patologia Sperimentali, Istituto di Anatomia Patologica, University of Florence, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Vannucchi
authors.forename: L
authors.initials: L
authors.lastname: Bianchi
authors.forename: C
authors.initials: C
authors.lastname: Cellai
authors.forename: F
authors.initials: F
authors.lastname: Paoletti
authors.forename: V
authors.initials: V
authors.lastname: Carrai
authors.forename: A
authors.initials: A
authors.lastname: Calzolari
authors.forename: L
authors.initials: L
authors.lastname: Centurione
authors.forename: R
authors.initials: R
authors.lastname: Lorenzini
authors.forename: C
authors.initials: C
authors.lastname: Carta
authors.forename: E
authors.initials: E
authors.lastname: Alfani
authors.forename: M
authors.initials: M
authors.lastname: Sanchez
authors.forename: G
authors.initials: G
authors.lastname: Migliaccio
authors.forename: A R
authors.initials: AR
authors.lastname: Migliaccio
mesh_terms: D000740:Anemia / Q000139:chemically induced; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D002452:Cell Count; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics*; D015672:Erythroid Precursor Cells / Q000473:pathology; D050981:Erythroid-Specific DNA-Binding Factors; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D050982:GATA1 Transcription Factor; D015870:Gene Expression; D006400:Hematocrit; D006412:Hematopoietic Stem Cells / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008533:Megakaryocytes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D010659:Phenylhydrazines / Q000494:pharmacology*; D010976:Platelet Count; D013154:Spleen / Q000473:pathology; D013921:Thrombocytopenia / Q000097:blood / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D010659:Phenylhydrazines; D014157:Transcription Factors; C030299:phenylhydrazine; D004921:Erythropoietin