GATA factor transgenes under GATA-1 locus control rescue germline GATA-1 mutant deficiencies.
Blood
; 96(3): 910-6, 2000 Aug 01.
Article
in En
| MEDLINE
| ID: mdl-10910904
ABSTRACT
GATA-1 germline mutation in mice results in embryonic lethality due to defective 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 properties or spatiotemporal patterning, we attempted to rescue GATA-1 mutant mice with hematopoietic GATA factor complementary DNAs (cDNAs) placed under 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 and GATA-3 factors expressed from the same regulatory cassette also rescued the embryonic lethal phenotype of the GATA-1 mutation. 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 critical determinant of GATA-1 activity during erythropoiesis. The results also show that there are biochemical distinctions among the hematopoietic GATA proteins and that during adult hematopoiesis the hematopoietic GATA factors are not functionally equivalent.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Trans-Activators
/
DNA-Binding Proteins
Limits:
Animals
Language:
En
Journal:
Blood
Year:
2000
Document type:
Article
Affiliation country:
Japan