Mouse ATF-2 null mutants display features of a severe type of meconium aspiration syndrome

Toshio Maekawa, François Bernier, Motohiko Sato, Shintaro Nomura, Mandavi Singh, Yoshiro Inoue, Tomoyuki Tokunaga, Hiroshi Imai, Minesuke Yokoyama, Andreas Reimold, Laurie H. Glimcher, Shunsuke Ishii

Research output: Contribution to journalArticle

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Abstract

Mouse null mutants of transcription factor ATF-2 were generated by the gene targeting method. They died shortly after birth and displayed symptoms of severe respiratory distress with lungs filled with meconium. These features are similar to those of a severe type of human meconium aspiration syndrome. The increased expression of the hypoxia inducible genes suggests that hypoxia occurs in the mutant embryos and that it may lead to strong gasping respiration with consequent aspiration of the amniotic fluid containing meconium. A reduced number of cytotrophoblast cells in the mutant placenta was found and may be responsible for an insufficient supply of oxygen prior to birth. Using the cDNA subtraction and microarray-based expression monitoring method, the expression level of the platelet-derived growth factor receptor α gene, which plays an important role in the proliferation of trophoblasts, was found to be low in the cytotrophoblasts of the mutant placenta. In addition, ATF-2 can trans-activate the PDGF receptor gene promoter in the co-transfection assay. These results indicate the important role of ATF-2 in the formation of the placenta and the relationship between placental anomalies and neonatal respiratory distress. The ATF-2 null mutants should enhance our understanding of the mechanism of severe neonatal respiratory distress.

Original languageEnglish (US)
Pages (from-to)17813-17819
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number25
DOIs
StatePublished - Jun 18 1999

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Meconium Aspiration Syndrome
Trophoblasts
Placenta
Platelet-Derived Growth Factor Receptors
Meconium
Genes
Activating Transcription Factors
Parturition
Gene Targeting
Amniotic Fluid
Oligonucleotide Array Sequence Analysis
Transfection
Respiration
Microarrays
Embryonic Structures
Cell Count
Oxygen
Assays
Lung
Complementary DNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

Maekawa, T., Bernier, F., Sato, M., Nomura, S., Singh, M., Inoue, Y., ... Ishii, S. (1999). Mouse ATF-2 null mutants display features of a severe type of meconium aspiration syndrome. Journal of Biological Chemistry, 274(25), 17813-17819. https://doi.org/10.1074/jbc.274.25.17813

Mouse ATF-2 null mutants display features of a severe type of meconium aspiration syndrome. / Maekawa, Toshio; Bernier, François; Sato, Motohiko; Nomura, Shintaro; Singh, Mandavi; Inoue, Yoshiro; Tokunaga, Tomoyuki; Imai, Hiroshi; Yokoyama, Minesuke; Reimold, Andreas; Glimcher, Laurie H.; Ishii, Shunsuke.

In: Journal of Biological Chemistry, Vol. 274, No. 25, 18.06.1999, p. 17813-17819.

Research output: Contribution to journalArticle

Maekawa, T, Bernier, F, Sato, M, Nomura, S, Singh, M, Inoue, Y, Tokunaga, T, Imai, H, Yokoyama, M, Reimold, A, Glimcher, LH & Ishii, S 1999, 'Mouse ATF-2 null mutants display features of a severe type of meconium aspiration syndrome', Journal of Biological Chemistry, vol. 274, no. 25, pp. 17813-17819. https://doi.org/10.1074/jbc.274.25.17813
Maekawa, Toshio ; Bernier, François ; Sato, Motohiko ; Nomura, Shintaro ; Singh, Mandavi ; Inoue, Yoshiro ; Tokunaga, Tomoyuki ; Imai, Hiroshi ; Yokoyama, Minesuke ; Reimold, Andreas ; Glimcher, Laurie H. ; Ishii, Shunsuke. / Mouse ATF-2 null mutants display features of a severe type of meconium aspiration syndrome. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 25. pp. 17813-17819.
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