Mice homozygous for a truncated form of CREB-binding protein exhibit defects in hematopoiesis and vasculo-angiogenesis

Yuichi Oike, Nobuyuki Takakura, Akira Hata, Tadashi Kaname, Miwa Akizuki, Yuji Yamaguchi, Hirofumi Yasue, Kimi Araki, Ken Ichi Yamamura, Toshio Suda

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

CREB-binding protein (CBP) and the closely related adenovirus E1A- associated 300-kD protein (p300) function as coactivators of transcription factors such as CREB, c-Fos, c-Jun, c-Myb, and several nuclear receptors. To study the roles of CBP in embryonic development, we generated CBP homozygous mutant mouse embryos that expressed a truncated form of CBP protein (1-1084 out of 2441 residues). The embryos died between embryonic days 9.5 (E9.5) and E10.5 and exhibited a defect in neural tube closure. They appeared pale and showed decreases in erythroid cells and colony-forming cells (CFCs) in the yolk sac, suggesting defects in primitive hematopoiesis. Immunohistochemistry with an anti-PECAM antibody showed a lack of vascular network formation. Organ culture of para-aortic splanchnopleural mesoderm (P-Sp) with stromal cells (OP9) showed an autonomous abnormality of putative endothelial precursors, which may induce the microenvironmental defect in hematopoiesis. In addition, these defects were partially rescued by the addition of VEGF to this culture. Our analyses demonstrate that CBP plays an essential role in hematopoiesis and vasculo-angiogenesis.

Original languageEnglish
Pages (from-to)2771-2779
Number of pages9
JournalBlood
Volume93
Issue number9
Publication statusPublished - 1999 May 1

Fingerprint

CREB-Binding Protein
Hematopoiesis
Defects
Embryonic Structures
Yolk Sac
Erythroid Cells
Neural Tube Defects
Organ Culture Techniques
Mesoderm
Cytoplasmic and Nuclear Receptors
Stromal Cells
Adenoviridae
Vascular Endothelial Growth Factor A
Embryonic Development
Blood Vessels
Anti-Idiotypic Antibodies
Proteins
Transcription Factors
Immunohistochemistry
Antibodies

ASJC Scopus subject areas

  • Hematology

Cite this

Oike, Y., Takakura, N., Hata, A., Kaname, T., Akizuki, M., Yamaguchi, Y., ... Suda, T. (1999). Mice homozygous for a truncated form of CREB-binding protein exhibit defects in hematopoiesis and vasculo-angiogenesis. Blood, 93(9), 2771-2779.

Mice homozygous for a truncated form of CREB-binding protein exhibit defects in hematopoiesis and vasculo-angiogenesis. / Oike, Yuichi; Takakura, Nobuyuki; Hata, Akira; Kaname, Tadashi; Akizuki, Miwa; Yamaguchi, Yuji; Yasue, Hirofumi; Araki, Kimi; Yamamura, Ken Ichi; Suda, Toshio.

In: Blood, Vol. 93, No. 9, 01.05.1999, p. 2771-2779.

Research output: Contribution to journalArticle

Oike, Y, Takakura, N, Hata, A, Kaname, T, Akizuki, M, Yamaguchi, Y, Yasue, H, Araki, K, Yamamura, KI & Suda, T 1999, 'Mice homozygous for a truncated form of CREB-binding protein exhibit defects in hematopoiesis and vasculo-angiogenesis', Blood, vol. 93, no. 9, pp. 2771-2779.
Oike Y, Takakura N, Hata A, Kaname T, Akizuki M, Yamaguchi Y et al. Mice homozygous for a truncated form of CREB-binding protein exhibit defects in hematopoiesis and vasculo-angiogenesis. Blood. 1999 May 1;93(9):2771-2779.
Oike, Yuichi ; Takakura, Nobuyuki ; Hata, Akira ; Kaname, Tadashi ; Akizuki, Miwa ; Yamaguchi, Yuji ; Yasue, Hirofumi ; Araki, Kimi ; Yamamura, Ken Ichi ; Suda, Toshio. / Mice homozygous for a truncated form of CREB-binding protein exhibit defects in hematopoiesis and vasculo-angiogenesis. In: Blood. 1999 ; Vol. 93, No. 9. pp. 2771-2779.
@article{025db2a8f372406c8cf7350fbc92c567,
title = "Mice homozygous for a truncated form of CREB-binding protein exhibit defects in hematopoiesis and vasculo-angiogenesis",
abstract = "CREB-binding protein (CBP) and the closely related adenovirus E1A- associated 300-kD protein (p300) function as coactivators of transcription factors such as CREB, c-Fos, c-Jun, c-Myb, and several nuclear receptors. To study the roles of CBP in embryonic development, we generated CBP homozygous mutant mouse embryos that expressed a truncated form of CBP protein (1-1084 out of 2441 residues). The embryos died between embryonic days 9.5 (E9.5) and E10.5 and exhibited a defect in neural tube closure. They appeared pale and showed decreases in erythroid cells and colony-forming cells (CFCs) in the yolk sac, suggesting defects in primitive hematopoiesis. Immunohistochemistry with an anti-PECAM antibody showed a lack of vascular network formation. Organ culture of para-aortic splanchnopleural mesoderm (P-Sp) with stromal cells (OP9) showed an autonomous abnormality of putative endothelial precursors, which may induce the microenvironmental defect in hematopoiesis. In addition, these defects were partially rescued by the addition of VEGF to this culture. Our analyses demonstrate that CBP plays an essential role in hematopoiesis and vasculo-angiogenesis.",
author = "Yuichi Oike and Nobuyuki Takakura and Akira Hata and Tadashi Kaname and Miwa Akizuki and Yuji Yamaguchi and Hirofumi Yasue and Kimi Araki and Yamamura, {Ken Ichi} and Toshio Suda",
year = "1999",
month = "5",
day = "1",
language = "English",
volume = "93",
pages = "2771--2779",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "9",

}

TY - JOUR

T1 - Mice homozygous for a truncated form of CREB-binding protein exhibit defects in hematopoiesis and vasculo-angiogenesis

AU - Oike, Yuichi

AU - Takakura, Nobuyuki

AU - Hata, Akira

AU - Kaname, Tadashi

AU - Akizuki, Miwa

AU - Yamaguchi, Yuji

AU - Yasue, Hirofumi

AU - Araki, Kimi

AU - Yamamura, Ken Ichi

AU - Suda, Toshio

PY - 1999/5/1

Y1 - 1999/5/1

N2 - CREB-binding protein (CBP) and the closely related adenovirus E1A- associated 300-kD protein (p300) function as coactivators of transcription factors such as CREB, c-Fos, c-Jun, c-Myb, and several nuclear receptors. To study the roles of CBP in embryonic development, we generated CBP homozygous mutant mouse embryos that expressed a truncated form of CBP protein (1-1084 out of 2441 residues). The embryos died between embryonic days 9.5 (E9.5) and E10.5 and exhibited a defect in neural tube closure. They appeared pale and showed decreases in erythroid cells and colony-forming cells (CFCs) in the yolk sac, suggesting defects in primitive hematopoiesis. Immunohistochemistry with an anti-PECAM antibody showed a lack of vascular network formation. Organ culture of para-aortic splanchnopleural mesoderm (P-Sp) with stromal cells (OP9) showed an autonomous abnormality of putative endothelial precursors, which may induce the microenvironmental defect in hematopoiesis. In addition, these defects were partially rescued by the addition of VEGF to this culture. Our analyses demonstrate that CBP plays an essential role in hematopoiesis and vasculo-angiogenesis.

AB - CREB-binding protein (CBP) and the closely related adenovirus E1A- associated 300-kD protein (p300) function as coactivators of transcription factors such as CREB, c-Fos, c-Jun, c-Myb, and several nuclear receptors. To study the roles of CBP in embryonic development, we generated CBP homozygous mutant mouse embryos that expressed a truncated form of CBP protein (1-1084 out of 2441 residues). The embryos died between embryonic days 9.5 (E9.5) and E10.5 and exhibited a defect in neural tube closure. They appeared pale and showed decreases in erythroid cells and colony-forming cells (CFCs) in the yolk sac, suggesting defects in primitive hematopoiesis. Immunohistochemistry with an anti-PECAM antibody showed a lack of vascular network formation. Organ culture of para-aortic splanchnopleural mesoderm (P-Sp) with stromal cells (OP9) showed an autonomous abnormality of putative endothelial precursors, which may induce the microenvironmental defect in hematopoiesis. In addition, these defects were partially rescued by the addition of VEGF to this culture. Our analyses demonstrate that CBP plays an essential role in hematopoiesis and vasculo-angiogenesis.

UR - http://www.scopus.com/inward/record.url?scp=0033134766&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033134766&partnerID=8YFLogxK

M3 - Article

VL - 93

SP - 2771

EP - 2779

JO - Blood

JF - Blood

SN - 0006-4971

IS - 9

ER -