Complexity of CNC transcription factors as revealed by gene targeting of the Nrf3 locus
Complexity of CNC transcription factors as revealed by gene targeting of the Nrf3 locus
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DOI：
10.1128/mcb.24.8.3286-3294.2004
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发表时间：
2004-04-01
影响因子：
5.3
通讯作者：
Blank, V
中科院分区：
文献类型：
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作者：
Derjuga, A;Gourley, TS;Blank, V
Cap'n'collar （CNC）家族亮氨酸拉链转录因子在哺乳动物基因表达和发育调控中起着至关重要的作用。为了确定CNC蛋白Nrf3 （nf - e2相关因子3）在体内的功能，我们制造了缺乏该转录因子的小鼠。我们对编码CNC同源性、基本dna结合和亮氨酸拉链二聚化结构域的两个Nrf3外显子进行了靶向破坏。Nrf3缺失小鼠发育正常，与野生型相比无明显表型差异。Nrf3（-/-）小鼠可生育，大体解剖和行为正常。小鼠表现出正常的年龄进展，并且在其一生中没有表现出任何明显的额外表型。我们观察到各种血液参数和化学值没有差异。我们用急性淋巴细胞性脉络丛脑膜炎病毒感染野生型和非rf（-/-）小鼠，发现这些动物在病毒特异性CD8和CD4 T细胞数量以及b淋巴细胞反应方面没有差异。为了确定Nrf3缺失动物的轻度表型是否是由于功能冗余，我们产生了多种CNC因子缺失的小鼠。与我们的预期相反，Nrf3的缺失似乎不会导致复合Nrf3(-/-)/Nrf2（-/-）和Nrf3(-/-)/p45（-/-）小鼠的额外致命性。我们假设Nrf3在体内的作用可能只有在适当的小鼠刺激后才会显现出来。
Cap'n'collar (CNC) family basic leucine zipper transcription factors play crucial roles in the regulation of mammalian gene expression and development. To determine the in vivo function of the CNC protein Nrf3 (NF-E2-related factor 3), we generated mice deficient in this transcription factor. We performed targeted disruption of two Nrf3 exons coding for CNC homology, basic DNA-binding, and leucine zipper dimerization domains. Nrf3 null mice developed normally and revealed no obvious phenotypic differences compared to wild-type animals. Nrf3(-/-) mice were fertile, and gross anatomy as well as behavior appeared normal. The mice showed normal age progression and did not show any apparent additional phenotype during their life span. We observed no differences in various blood parameters and chemistry values. We infected wild-type and Nrf(-/-) mice with acute lymphocytic choriomeningitis virus and found no differences in these animals with respect to their number of virus-specific CD8 and CD4 T cells as well as their B-lymphocyte response. To determine whether the mild phenotype of Nrf3 null animals is due to functional redundancy, we generated mice deficient in multiple CNC factors. Contrary to our expectations, an absence of Nrf3 does not seem to cause additional lethality in compound Nrf3(-/-)/Nrf2(-/-) and Nrf3(-/-)/p45(-/-) mice. We hypothesize that the role of Nrf3 in vivo may become apparent only after appropriate challenge to the mice.