Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis

Pandolfi, Pier Paolo; Roth, Matthew E.; Karis, Alar; Leonard, Mark; Dzierzak, Elaine; Grosveld, Frank; Engel, James Douglas; Lindenbaum, Michael

doi:10.1038/ng0995-40

Cited by 556 publications

(420 citation statements)

References 31 publications

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“…Part of the difficulty in doing so is that deleting Gata3 results in embryonic lethality [40]. Furthermore, GATA-3 is involved in multiple stages of CD4 T cell development.…”

Section: The Central Role Of Gata-3 In Reinforcing Th2 Responsesmentioning

confidence: 99%

GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors

et al. 2006

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Naïve CD4 T cells can differentiate into at least two different types of T helpers, Th1 and Th2 cells. Th2 cells, capable of producing IL-4, IL-5 and IL-13, are involved in humoral immunity against extracellular pathogens and in the induction of asthma and other allergic diseases. In this review, we summarize recent reports regarding the transcription factors involved in Th2 differentiation and cell expansion, including Stat5, Gfi-1 and GATA-3. Stat5 activation is necessary and sufficient for IL-2-mediated function in Th2 differentiation. Enhanced Stat5 signaling induces Th2 differentiation independent of IL-4 signaling; although it does not up-regulate GATA-3 expression, it does require the presence of GATA-3 for its action. Gfi-1, induced by IL-4, promotes the expansion of GATA-3-expressing cells. Analysis of conditional Gata3 knockout mice confirmed the critical role of GATA-3 in Th2 cell differentiation (both IL-4 dependent and IL-4 independent) and in Th2 cell proliferation and also showed the importance of basal GATA-3 expression in inhibiting Th1 differentiation.

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“…Part of the difficulty in doing so is that deleting Gata3 results in embryonic lethality [40]. Furthermore, GATA-3 is involved in multiple stages of CD4 T cell development.…”

Section: The Central Role Of Gata-3 In Reinforcing Th2 Responsesmentioning

confidence: 99%

GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors

et al. 2006

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“…These include neurons of the sympathetic nervous system, T helper cells, the inner root sheath of hair follicles, fat cells, nephritic ducts of the kidney, and the ear cochleae [4,5]. Fetal mice cannot survive to term without GATA3 [6]. In humans, mutations in one of the GATA3 genes lead to thyroid and kidney dysfunctions, and hearing abnormalities [7].…”

Section: Introductionmentioning

confidence: 99%

The significance of GATA3 expression in breast cancer: a 10-year follow-up study

Ciocca¹,

Daskalakis²,

Ciocca³

et al. 2009

Human Pathology

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“…The embryonic lethality of Gata3 -/-mutant mice at day 11 of gestation [8] and the failure of Gata3 -/-ES cells to contribute to the T cell compartment in Rag2 -/-or WT chimeric mice [5,9] precluded the analysis of GATA3 function in murine T cell development in vivo. Conditional deletion of the Gata3 gene at the DN stage using the Cre-loxP system, whereby the Cre transgene was driven by the proximal Lck promoter, resulted in a developmental arrest at the CD25 + CD44 -DN3 stage, implicating GATA3 in b-selection [10].…”

Section: Introductionmentioning

confidence: 99%

GATA3 controls the expression of CD5 and the T cell receptor during CD4 T cell lineage development

et al. 2007

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The transcription factor GATA3 is essential at multiple stages of T cell development, including the earliest double-negative stages, b-selection and CD4 single-positive thymocytes. Here, we show that in CD2-GATA3 transgenic mice, with enforced GATA3 expression driven by the CD2 promoter, thymocytes have reduced levels of CD5, which is a negative regulator of TCR signaling participating in TCR repertoire fine-tuning. Reduction of CD5 expression was most prominent in CD4 + CD8 + double-positive (DP) cells and was associated with increased levels of the transcription factor E2A. Conversely, GATA3-deficient DP thymocytes showed consistently higher CD5 levels and defective TCR up-regulation during their development towards the CD4 lo CD8 lo subpopulation. CD2-GATA3 transgenic mice carrying the MHC class II-restricted TCR DO11.10 also manifested decreased CD5 levels. As in these TCR-transgenic mice reduced CD5 expression cannot result from an effect of GATA3 on repertoire selection, we conclude that enforced GATA3 interferes with the developmentally regulated increase of CD5 levels. Enforced GATA3 expression in DO11.10 transgenic mice was also accompanied by enhanced TCR expression during CD4 positive selection. Because GATA3 is induced by TCR signaling in DP thymocytes, our findings indicate that GATA3 establishes a positive feedback loop that increases TCR surface expression in developing CD4 lineage cells.

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Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis

Cited by 556 publications

References 31 publications

GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors

GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors

The significance of GATA3 expression in breast cancer: a 10-year follow-up study

GATA3 controls the expression of CD5 and the T cell receptor during CD4 T cell lineage development

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