Rescue of the embryonic lethal hematopoietic defect reveals a critical role for GATA-2 in urogenital development

Yinghui Zhou, Kim Chew Lim, Ko Onodera, Satoru Takahashi, Jun Ohta, Naoko Minegishi, Fong Ying Tsai, Stuart H. Orkin, Masayuki Yamamoto, James Douglas Engel

研究成果: Article査読

119 被引用数 (Scopus)

抄録

Mutations resulting in embryonic or early postnatal lethality could mask the activities of any gene in unrelated and temporally distinct developmental pathways. Targeted inactivation of the transcription factor GATA-2 gene leads to mid-gestational death as a consequence of hematopoietic failure. We show here that a 250 kbp GATA-2 yeast artificial chromosome (YAC) is expressed strongly in both the primitive and definitive hematopoietic compartments, while two smaller YACs are not. This largest YAC also rescues hematopoiesis in vitro and in vivo, thereby localizing the hematopoietic regulatory cis element(s) to between 100 and 150 kbp 5' to the GATA-2 structural gene. Introducing the YAC transgene into the GATA-2(-/-) genetic background allows the embryos to complete gestation; however, newborn rescued pups quickly succumb to lethal hydroureternephrosis, and display a complex array of genitourinary abnormalities. These findings reveal that GATA-2 plays equally vital roles in urogenital and hematopoietic development.

本文言語English
ページ(範囲)6689-6700
ページ数12
ジャーナルEMBO Journal
17
22
DOI
出版ステータスPublished - 1998 11 16
外部発表はい

ASJC Scopus subject areas

  • 神経科学(全般)
  • 分子生物学
  • 生化学、遺伝学、分子生物学(全般)
  • 免疫学および微生物学(全般)

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