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Blood, 15 May 2001, Vol. 97, No. 10, pp. 3040-3050
HEMATOPOIESIS
Accentuated response to phenylhydrazine and
erythropoietin in mice genetically impaired for their GATA-1 expression
(GATA-1low mice)
Alessandro Maria Vannucchi,
Lucia Bianchi,
Cristina Cellai,
Francesco Paoletti,
Valentina Carrai,
Anna Calzolari,
Lucia Centurione,
Rodolfo Lorenzini,
Claudio Carta,
Elena Alfani,
Massimo Sanchez,
Giovanni Migliaccio, and
Anna Rita Migliaccio
From the Department of Hematology and Istituto di
Oncologia and Patologia Sperimentali, Istituto di Anatomia Patologica,
University of Florence, and Azienda Ospedaliera Careggi, Florence;
Dipartimento di Biomorfologia, Università G. D'Annunzio, Chieti;
and Servizio di Qualità and Sicurezza della Sperimentazione
Animale, Laboratorio di Biologia Cellulare, and di Biochimica Clinica,
Istituto Superiore di Sanità, Rome, Italy.
The response of mice genetically unable to up-regulate GATA-1
expression (GATA-1low 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-1low mice
are profoundly thrombocytopenic (platelet counts
[× 109/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-1low 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-1low 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-1low 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-1low mutation
increases the magnitude of the response to erythroid stimuli as a
consequence of the expansion of the erythroid progenitor cells in their spleen.
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