Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-2910, USA.
Cells. 2024 Jun 28;13(13):1123. doi: 10.3390/cells13131123.
Mating in female causes midgut hypertrophy and reduced lifespan, and these effects are blocked by the drug mifepristone. Eip75B is a transcription factor previously reported to have pleiotropic effects on lifespan. Because Eip75B null mutations are lethal, conditional systems and/or partial knock-down are needed to study Eip75B effects in adults. Previous studies showed that Eip75B is required for adult midgut cell proliferation in response to mating. To test the possible role of Eip75B in mediating the lifespan effects of mating and mifepristone, a tripartite FLP-recombinase-based conditional system was employed that provides controls for genetic background. Expression of a transgene was induced in third instar larvae by a brief heat pulse. The FLP recombinase catalyzed the recombination and activation of an transgene. The GAL4 transcription factor in turn activated expression of a transgene. Inhibition of Eip75B activity was confirmed by loss of midgut hypertrophy upon mating, and the lifespan effects of both mating and mifepristone were eliminated. In addition, the negative effects of mifepristone on egg production were eliminated. The data indicate that Eip75B mediates the effects of mating and mifepristone on female midgut hypertrophy, egg production, and lifespan.
在雌性中交配会导致中肠肥大和寿命缩短，这些影响可以被药物米非司酮阻断。Eip75B 是一种先前被报道对寿命具有多效性影响的转录因子。由于 Eip75B 缺失突变是致命的，因此需要条件系统和/或部分敲低来研究 Eip75B 在成年期的作用。先前的研究表明，Eip75B 是交配诱导成年中肠细胞增殖所必需的。为了测试 Eip75B 在介导交配和米非司酮对寿命影响中的可能作用，使用了一种基于三部分 FLP 重组酶的条件系统，该系统为遗传背景提供了对照。通过短暂的热脉冲在三龄幼虫中诱导表达一个 转座子。FLP 重组酶催化 转座子的重组和激活。GAL4 转录因子反过来激活了 转座子的表达。交配导致中肠肥大，Eip75B 活性受到抑制，交配和米非司酮的寿命效应都被消除。此外，米非司酮对产卵的负面影响也被消除。这些数据表明，Eip75B 介导了交配和米非司酮对雌性中肠肥大、产卵和寿命的影响。
