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

Dev Biol. 2007 Jan 15;301(2):568-77. doi: 10.1016/j.ydbio.2006.09.030. Epub 2006 Sep 22.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Embryo, Mammalian / embryology
  • Embryo, Mammalian / metabolism
  • Enhancer Elements, Genetic / genetics*
  • Female
  • GATA3 Transcription Factor / deficiency
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / metabolism*
  • Gene Expression Regulation, Developmental / genetics
  • Genotype
  • Kidney / embryology*
  • Kidney / metabolism*
  • Male
  • Mice
  • Mice, Transgenic
  • Mutation / genetics
  • Phenotype
  • Transgenes / genetics


  • GATA3 Transcription Factor
  • Gata3 protein, mouse