Targeted disruption of the activating transcription factor 4 gene results in severe fetal anemia in mice

Howard Masuoka, Tim M. Townes

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

Activating transcription factor (ATF) 4 is a ubiquitous basic leucine-zipper transcription factor that is a member of the ATF/ cyclic adenosine monophosphate responsive element-binding (CREB) protein family. To determine the in vivo function of ATF4, the ATF4 gene in murine embryonic stem cells was deleted and homozygous mutant mice were generated. ATF4 null fetuses were severely anemic because of an impairment in fetal-liver definitive hematopoiesis; the hematocrit in 15.5-day mutant fetuses was 0.15, whereas that in controls was 0.35. The fetal livers in homozygous ATF4 mutants were pale and hypoplastic. In vitro culture of fetal-liver cells showed fewer hematopoietic progenitors per embryo and a dramatic decrease in the size of progenitor colonies. Culture of primary murine embryonic fibroblasts showed a proliferative defect. These results suggest that ATF4 is critical, in a cell-autonomous manner, for normal cellular proliferation, especially for the high-level proliferation required during fetal-liver hematopoiesis.

Original languageEnglish (US)
Pages (from-to)736-745
Number of pages10
JournalBlood
Volume99
Issue number3
DOIs
StatePublished - Feb 1 2002
Externally publishedYes

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Activating Transcription Factor 4
Liver
Anemia
Genes
Hematopoiesis
Fetus
Activating Transcription Factors
Basic-Leucine Zipper Transcription Factors
Fibroblasts
Embryonic Stem Cells
Stem cells
Hematocrit
Cell culture
Cyclic AMP
Carrier Proteins
Embryonic Structures
Cell Proliferation
Defects

ASJC Scopus subject areas

  • Hematology

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Targeted disruption of the activating transcription factor 4 gene results in severe fetal anemia in mice. / Masuoka, Howard; Townes, Tim M.

In: Blood, Vol. 99, No. 3, 01.02.2002, p. 736-745.

Research output: Contribution to journalArticle

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