编码肝细胞核因子3γ的基因的靶向破坏导致肝细胞特异性基因的转录减少。
Targeted disruption of the gene encoding hepatocyte nuclear factor 3gamma results in reduced transcription of hepatocyte-specific genes.
作者信息
Kaestner K H, Hiemisch H, Schütz G
机构信息
Department of Genetics, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104-6145, USA.
出版信息
Mol Cell Biol. 1998 Jul;18(7):4245-51. doi: 10.1128/MCB.18.7.4245.
Abstract
The winged helix transcription factor hepatocyte nuclear factor 3gamma (HNF3gamma) is expressed in embryonic endoderm and its derivatives liver, pancreas, stomach, and intestine, as well as in testis and ovary. We have generated mice carrying an Hnf3g-lacZ fusion which deletes most of the HNF3gamma coding sequence as well as 5.5 kb of 3' flanking region. Mice homozygous for the mutation are fertile, develop normally, and show no morphological defects. The mild phenotype change of the Hnf3g-/- mice can be explained in part by an upregulation of HNF3alpha and HNF3beta in the liver of the mutant animals. Analysis of steady-state mRNA levels as well as transcription rates showed that levels of expression of several HNF3 target genes (phosphoenolpyruvate carboxykinase, transferrin, tyrosine aminotransferase) were reduced by 50 to 70%, indicating that HNF3gamma is an important activator of these genes in vivo.
摘要
翼状螺旋转录因子肝细胞核因子3γ（HNF3γ）在胚胎内胚层及其衍生物肝脏、胰腺、胃和肠道以及睾丸和卵巢中表达。我们构建了携带Hnf3g - lacZ融合基因的小鼠，该融合基因删除了大部分HNF3γ编码序列以及5.5 kb的3'侧翼区域。该突变的纯合子小鼠可育，发育正常，且未表现出形态学缺陷。Hnf3g - / - 小鼠的轻微表型变化部分可通过突变动物肝脏中HNF3α和HNF3β的上调来解释。对稳态mRNA水平以及转录速率的分析表明，几个HNF3靶基因（磷酸烯醇丙酮酸羧激酶、转铁蛋白、酪氨酸转氨酶）的表达水平降低了50%至70%，这表明HNF3γ在体内是这些基因的重要激活因子。
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本文引用的文献
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