Gata4 is essential for the maintenance of Jejunal-Ileal identities in the adult mouse small intestine
Gata4 is essential for the maintenance of Jejunal-Ileal identities in the adult mouse small intestine
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DOI：
10.1128/mcb.00124-06
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发表时间：
2006-12-01
影响因子：
5.3
通讯作者：
Krasinski, Stephen D.
中科院分区：
文献类型：
--
作者：
Bosse, Tjalling;Piaseckyj, Christina M.;Krasinski, Stephen D.
Gata 4是加塔转录因子锌指家族的成员，在成年小鼠的十二指肠和空肠中高度表达，但在回肠末端几乎检测不到。我们在这里表明，Gata 4的尾部减少在人类中是保守的。为了验证Gata 4的区域表达对于维持体内成人小肠中空回肠稳态至关重要的假设，我们建立了一种诱导型的、精氨酸特异性的模型，该模型导致合成转录失活的Gata 4突变体。在6- 8周龄小鼠的空肠中合成突变体Gata 4导致通常在空肠中表达但在回肠中不表达的吸收性肠上皮细胞基因的减弱，包括预期靶点肝脂肪酸结合蛋白（Fabp 1）和乳糖酶-根皮苷水解酶（LPH）的基因，以及通常在空肠中沉默但在回肠中高度表达的基因的令人惊讶的诱导，特别是那些参与胆汁酸转运的。Gata 4的失活导致杯状细胞群的增加和肠内分泌亚群的重新分布，全部朝向回肠表型。编码Math 1（一种已知的分泌细胞命运的激活剂）的基因被诱导类似于75%（P < 0.05）。因此，Gata 4是维持成年小鼠小肠空肠-回肠特性所需的重要位置信号。
Gata4, a member of the zinc finger family of GATA transcription factors, is highly expressed in duodenum and jejunum but is nearly undetectable in distal ileum of adult mice. We show here that the caudal reduction of Gata4 is conserved in humans. To test the hypothesis that the regional expression of Gata4 is critical for the maintenance of jejunal-ileal homeostasis in the adult small intestine in vivo, we established an inducible, intestine-specific model that results in the synthesis of a transcriptionally inactive Gata4 mutant. Synthesis of mutant Gata4 in jejuna of 6- to 8-week-old mice resulted in an attenuation of absorptive enterocyte genes normally expressed in jejunum but not in ileum, including those for the anticipated targets liver fatty acid binding protein (Fabp1) and lactase-phlorizin hydrolase (LPH), and a surprising induction of genes normally silent in jejunum but highly expressed in ileum, specifically those involved in bile acid transport. Inactivation of Gata4 resulted in an increase in the goblet cell population and a redistribution of the enteroendocrine subpopulations, all toward an ileal phenotype. The gene encoding Math1, a known activator of the secretory cell fate, was induced similar to 75% (P < 0.05). Gata4 is thus an important positional signal required for the maintenance of jejunal-ileal identities in the adult mouse small intestine.