期刊
DEVELOPMENTAL BIOLOGY
卷 301, 期 2, 页码 568-577出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2006.09.030
关键词
Gata3; kidney; rescue; enhancer; allelic series; haploinsufficiency
资金
- NCI NIH HHS [CA46592, P30 CA046592] Funding Source: Medline
- NIGMS NIH HHS [R01 GM028896, GM28896] Funding Source: Medline
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 transgenie 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. (c) 2006 Elsevier Inc. All rights reserved.
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