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

S. Takahashi, R. Shimizu, N. Suwabe, T. Kuroha, K. Yoh, J. Ohta, S. Nishimura, K. C. Lim, J. D. Engel, M. Yamamoto

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Abstract

GATA-1 germline mutation in mice results in embryonic lethality due to defective erythroid cell maturation, and thus other hematopoletic 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 spatio-temporal 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 hemetopoietic GATA factors are not functionally equivalent. (C) 2000 by The American Society of Hematology.

Original languageEnglish
Pages (from-to)910-916
Number of pages7
JournalBlood
Volume96
Issue number3
DOIs
Publication statusPublished - 2000 Aug 1

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Takahashi, S., Shimizu, R., Suwabe, N., Kuroha, T., Yoh, K., Ohta, J., Nishimura, S., Lim, K. C., Engel, J. D., & Yamamoto, M. (2000). GATA factor transgenes under GATA-1 locus control rescue germline GATA-1 mutant deficiencies. Blood, 96(3), 910-916. https://doi.org/10.1182/blood.v96.3.910.015k29_910_916