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首页> 外文期刊>Molecular and Cellular Biology >Tissue-Specific Transgenic Knockdown of Fos-Related Antigen 2 (Fra-2) Expression Mediated by Dominant Negative Fra-2
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Tissue-Specific Transgenic Knockdown of Fos-Related Antigen 2 (Fra-2) Expression Mediated by Dominant Negative Fra-2

机译：组织负特异性Fra-2介导的Fos相关抗原2（Fra-2）表达的组织特异性转基因敲低。

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Fos-related antigen 2 (Fra-2) is a member of the Fos family of immediate-early genes, most of which are rapidly induced by second messengers. All members of this family act by binding to AP-1 sites as heterodimeric complexes with other proteins. However, each appears to have a distinct role. The role and biology of Fra-2 are less well understood than those of its relatives c-Fos, Fra-1, and FosB; moreover, Fra-2 target genes remain largely unknown, as does the basis of its selective effects on transcriptional activity. To pursue these issues, we created a transgenic rat line (NATDNF2) in which a dominant negative fra-2 (DNF2) gene is strongly expressed in the pineal gland; tissue selectivity was achieved by putting the DNF2 gene under the control of the rat arylalkylamineN-acetyltransferase (AANAT) regulatory region, which targets gene expression to a very restricted set of tissues (pineal gland ? retina). Expression of AANAT is normally turned on after the onset of darkness in the rat; as a result, pineal DNF2 expression occurs only at night. This was associated with marked suppression of the nocturnal increase in fra-2 mRNA and protein levels, indicating that DNF2 expression inhibits downstream effects of Fra-2, including the maintenance of high levels offra-2 gene expression. Analysis of 1,190 genes in the NATDNF2 pineal gland, including the AANAT gene, identified two whose expression is strongly linked to fra-2 expression: the genes encoding type II iodothyronine deiodinase and nectadrin (CD24).
机译：Fos相关抗原2（Fra-2）是Fos家族的即早基因家族的成员，其中大多数由第二信使迅速诱导。该家族的所有成员通过与其他蛋白质的异二聚体复合物结合到AP-1位点而发挥作用。但是，每个似乎都有不同的作用。与其亲戚c-Fos，Fra-1和FosB相比，对Fra-2的作用和生物学了解较少。此外，Fra-2靶基因以及其对转录活性的选择性作用基础仍然是很大程度上未知的。为了解决这些问题，我们创建了一个转基因大鼠品系（NATDNF2），其中显性负性 fra-2 （DNF2）基因在松果体中强烈表达。通过将DNF2基因置于大鼠芳基烷基胺 N -乙酰基转移酶（AANAT）调控区域的控制下，可以实现组织选择性，该调控区域将基因表达的靶标限制在非常有限的组织（松果体-视网膜）上。通常在大鼠黑暗开始后，AANAT的表达才会开启。结果，松果体DNF2表达仅在晚上发生。这与 fra-2 mRNA和蛋白质水平的夜间增加明显抑制有关，表明DNF2表达抑制Fra-2的下游作用，包括维持高水平的 fra- 2 基因表达。分析了NATDNF2松果体中的1,190个基因，包括AANAT基因，确定了两个表达与 fra-2 表达紧密相关的基因：编码II型碘甲状腺素脱碘酶和nectadrin（CD24）的基因。

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