Dosage-dependent rescue of definitive nephrogenesis by a distant Gata3 enhancer

Susan L. Hasegawa, Takashi Moriguchi, Arvind Rao, Takashi Kuroha, James Douglas Engel, Kim Chew Lim

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


Human GATA3 haploinsufficiency leads to HDR (hypoparathyroidism, deafness and renal dysplasia) syndrome, demonstrating that the development of a specific subset of organs in which this transcription factor is expressed is exquisitely sensitive to gene dosage. We previously showed that murine GATA-3 is essential for definitive kidney development, and that a large YAC transgene faithfully recapitulated GATA-3 expression in the urogenital system. Here we describe the localization and activity of a kidney enhancer (KE) located 113 kbp 5′ to the Gata3 structural gene. When the KE was employed to direct renal system-specific GATA-3 transcription, the extent of cell autonomous kidney rescue in Gata3-deficient mice correlated with graded allelic expression of transgenic GATA-3. These data demonstrate that a single distant, tissue-specific enhancer can direct GATA-3 gene expression to confer all embryonic patterning information that is required for successful execution of metanephrogenesis, and that the dosage of GATA-3 required has a threshold between 50% and 70% of diploid activity.

Original languageEnglish
Pages (from-to)568-577
Number of pages10
JournalDevelopmental Biology
Issue number2
Publication statusPublished - 2007 Jan 15
Externally publishedYes


  • Allelic series
  • Enhancer
  • Gata3
  • Haploinsufficiency
  • Kidney
  • Rescue

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


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