Disease relevance of Gata3

• Hearing loss following Gata3 haploinsufficiency is caused by cochlear disorder [1].
• Whereas Gata2 is predominantly expressed in the dorsal vestibular system, Gata3 was detected mainly in the ventral cochlear duct and ganglion [2].

High impact information on Gata3

• We recently showed that Gata3-directed lacZ expression of a 625-kb Gata3 YAC transgene in mice mimics endogenous Gata3 expression, except in thymus and the sympathoadrenal system [3].
• As this transgene failed to overcome embryonic lethality (unpublished data and ref. 3) in Gata3-/- mice, we hypothesized that a neuroendocrine deficiency in the sympathetic nervous system (SNS) might cause embryonic lethality in these mutants [3].
• Thus we have shown that Gata3 has a role in the differentiation of multiple cell lineages during embryogenesis [3].
• In vivo deletion of Gata3 using OX40-Cre eliminated T(H)2 responses and allowed the development of interferon-gamma-producing cells in mice infected with Nippostrongylus brasiliensis [4].
• Gata-3 functions, in part, to displace MBD2 from methylated DNA [5].

Biological context of Gata3

• However, SA lineage-specific restoration of Gata3 function in the Gata3 mutant background rescues the expression phenotypes of the downstream, as well as the putative upstream genes [6].
• In Gata3-null embryos, there was significant impairment of SA differentiation and increased apoptosis in adrenal chromaffin cells and sympathetic neurons [6].
• Auditory brainstem response (ABR) thresholds of alert heterozygous Gata3 mice, analyzed from 1 to 19 months of age, showed a hearing loss of 30 dB compared to wild-type littermates [1].
• Ear morphogenesis is blocked in Gata3-deficient embryos, whereas nothing was known of the role of Gata2 in mouse inner ear [2].
• Gene expression analysis of Gata3-/- mice by using cDNA microarray technology [7].

Anatomical context of Gata3

• Gata3 loss leads to embryonic lethality due to noradrenaline deficiency of the sympathetic nervous system [3].
• In contrast, cochleae of heterozygous Gata3 mice showed significant progressive morphological degeneration starting with the outer hair cells (OHCs) at the apex and ultimately affecting all hair cells and supporting cells in the entire cochlea [1].
• The Gata3 gene is one of the earliest markers for the developing mouse inner ear [2].
• This study revealed that the sites, where Dab2 is downregulated in the mutant embryos partly overlap with the Gata3 expression domains, including the mid-embryo region, branchial arches and facio-acoustic (VII-VIII) neural crest complex [7].
• Transcriptome and phenotypic analysis reveals Gata3-dependent signalling pathways in murine hair follicles [8].

Associations of Gata3 with chemical compounds

• We then measured serum urea levels, performed histomorphometric analysis for tubular necrosis and regeneration, and evaluated the mRNA expression of HO-1, t-bet, Gata-3 and MCP-1 by real-time PCR at 24, 48 and 120 h after surgery [9].

Regulatory relationships of Gata3

• Pax 2/8-regulated Gata 3 expression is necessary for morphogenesis and guidance of the nephric duct in the developing kidney [10].
• AIM: To investigate effects of CpG oligodeoxynucleotide (CpG ODN) on the mRNA expression of transcription factors GATA binding protein 3 (GATA-3) and T-box expressed in T cells (T-bet) in asthmatic mice [11].

Other interactions of Gata3

• No phenotypic abnormalities were observed in the inner ear of Gata2-/- embryos before lethality at E10.5 and Gata3 expression was unchanged [2].
• This is the first time when tumor supressor gene Dab2 is shown to be implicated in the defective phenotype of Gata3 mutant mice [7].
• At the molecular level, the nephric duct of Gata 3(-/-) embryos is characterized by the loss of Ret expression and signaling, which may contribute to the guidance defect of the nephric duct [10].
• Gata3 is required for early morphogenesis and Fgf10 expression during otic development [12].
• Finally, PG102T and PG102E downregulated the level of GATA-binding protein 3, while inducing that of T-box transcription factor and nuclear factor of activated T cells c2 [13].

References