小鼠模型中的雌激素受体融合系统：一种可逆开关。
The estrogen receptor fusion system in mouse models: a reversible switch.
作者信息
Whitfield Jonathan, Littlewood Trevor, Evan Gerard I, Soucek Laura
机构信息
Vall d'Hebron Institute of Oncology (VHIO), Barcelona 08035, Spain; Universitat Autònoma de Barcelona, 08193 Bellaterra (Cerdanyola del Vallès), Spain;
Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
出版信息
Cold Spring Harb Protoc. 2015 Mar 2;2015(3):227-34. doi: 10.1101/pdb.top069815.
Abstract
Reversible regulatory mouse models have significantly contributed to our understanding of normal tissue and cancer biology, providing the opportunity to temporally control initiation, progression, and evolution of physiological and pathological events. The tamoxifen inducible system, one of the best-characterized "reversible switch" models, has a number of beneficial features. In this system, the hormone-binding domain of the mammalian estrogen receptor is used as a heterologous regulatory domain. Upon ligand binding, the receptor is released from its inhibitory complex and the fusion protein becomes functional. We summarize the advantages and drawbacks of the system, describe several mouse models that rely on it, and discuss potential improvements that could render it even more useful and versatile.
摘要
可逆调控小鼠模型对我们理解正常组织和癌症生物学做出了重大贡献，为暂时控制生理和病理事件的起始、进展和演变提供了机会。他莫昔芬诱导系统是特征最明确的“可逆开关”模型之一，具有许多有益特性。在该系统中，哺乳动物雌激素受体的激素结合结构域被用作异源调控结构域。配体结合后，受体从其抑制复合物中释放出来，融合蛋白变得具有功能。我们总结了该系统的优缺点，描述了几种依赖于它的小鼠模型，并讨论了可能使其更有用和更通用的潜在改进。
相似文献
1
The estrogen receptor fusion system in mouse models: a reversible switch.小鼠模型中的雌激素受体融合系统：一种可逆开关。
Cold Spring Harb Protoc. 2015 Mar 2;2015(3):227-34. doi: 10.1101/pdb.top069815.
2
Tamoxifen administration to mice.对小鼠给予他莫昔芬。
Cold Spring Harb Protoc. 2015 Mar 2;2015(3):269-71. doi: 10.1101/pdb.prot077966.
3
FLP recombinase/estrogen receptor fusion proteins require the receptor D domain for responsiveness to antagonists, but not agonists.FLP重组酶/雌激素受体融合蛋白对拮抗剂的反应性需要受体D结构域，但对激动剂则不需要。
Mol Endocrinol. 1997 Jun;11(7):950-61. doi: 10.1210/mend.11.7.9944.
4
A modified oestrogen receptor ligand-binding domain as an improved switch for the regulation of heterologous proteins.一种经过修饰的雌激素受体配体结合结构域，作为调控异源蛋白的改良开关。
Nucleic Acids Res. 1995 May 25;23(10):1686-90. doi: 10.1093/nar/23.10.1686.
5
Identification of tamoxifen-induced coregulator interaction surfaces within the ligand-binding domain of estrogen receptors.他莫昔芬诱导的雌激素受体配体结合域内共调节因子相互作用表面的鉴定。
Mol Cell Biol. 2004 Apr;24(8):3445-59. doi: 10.1128/MCB.24.8.3445-3459.2004.
6
A tamoxifen inducible knock-in allele for investigation of E2A function.用于研究E2A功能的他莫昔芬诱导型敲入等位基因。
BMC Dev Biol. 2009 Oct 12;9:51. doi: 10.1186/1471-213X-9-51.
7
Yeast two-hybrid system demonstrates that estrogen receptor dimerization is ligand-dependent in vivo.酵母双杂交系统表明，雌激素受体二聚化在体内是依赖配体的。
J Biol Chem. 1995 Oct 6;270(40):23322-9. doi: 10.1074/jbc.270.40.23322.
8
Structural requirements for high affinity ligand binding by estrogen receptors: a comparative analysis of truncated and full length estrogen receptors expressed in bacteria, yeast, and mammalian cells.
Mol Endocrinol. 1992 Jun;6(6):861-9. doi: 10.1210/mend.6.6.1495491.
9
Spatio-temporally controlled site-specific somatic mutagenesis in the mouse.小鼠体内时空控制的位点特异性体细胞诱变
Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14559-63. doi: 10.1073/pnas.94.26.14559.
10
Tamoxifen-inducible Cre-mediated recombination in adipocytes.他莫昔芬诱导的脂肪细胞中 Cre 介导的重组。
Genesis. 2010 Oct 1;48(10):618-25. doi: 10.1002/dvg.20665.
引用本文的文献
1
The Complementary Role of Morphology in Understanding Microglial Functional Heterogeneity.形态学在理解小胶质细胞功能异质性中的补充作用。
Int J Mol Sci. 2025 Apr 17;26(8):3811. doi: 10.3390/ijms26083811.
2
Sleep Deprivation Alters Hippocampal Dendritic Spines in a Contextual Fear Memory Engram.睡眠剥夺会改变情境恐惧记忆印迹中的海马树突棘。
bioRxiv. 2025 Mar 5:2025.03.02.641043. doi: 10.1101/2025.03.02.641043.
3
Foxg1 regulates translation of neocortical neuronal genes, including the main NMDA receptor subunit gene, Grin1.Foxg1 调控新皮层神经元基因的翻译，包括主要的 NMDA 受体亚基基因 Grin1。
BMC Biol. 2024 Aug 26;22(1):180. doi: 10.1186/s12915-024-01979-x.
4
Mouse models of diffuse large B cell lymphoma.弥漫性大 B 细胞淋巴瘤的小鼠模型。
Front Immunol. 2023 Dec 6;14:1313371. doi: 10.3389/fimmu.2023.1313371. eCollection 2023.
5
Region-specific targeting of microglia in vivo using direct delivery of tamoxifen metabolites via microfluidic polymer fibers.通过微流控聚合物纤维直接递送他莫昔芬代谢物在体内对小胶质细胞进行区域特异性靶向。
Brain Behav Immun. 2024 Jan;115:131-142. doi: 10.1016/j.bbi.2023.09.021. Epub 2023 Oct 17.
6
Evolution by innovation as a driving force to improve TCR-T therapies.通过创新实现进化作为改善TCR-T疗法的驱动力。
Front Oncol. 2023 Sep 21;13:1216829. doi: 10.3389/fonc.2023.1216829. eCollection 2023.
7
Advances in Immunocompetent Mouse and Rat Models.免疫活性小鼠和大鼠模型的进展
Cold Spring Harb Perspect Med. 2024 Mar 1;14(3):a041328. doi: 10.1101/cshperspect.a041328.
8
Developing Bottom-Up Induced Pluripotent Stem Cell Derived Solid Tumor Models Using Precision Genome Editing Technologies.利用精确基因组编辑技术开发基于底部的诱导多能干细胞衍生的实体瘤模型。
CRISPR J. 2022 Aug;5(4):517-535. doi: 10.1089/crispr.2022.0032.
9
The Akt Forkhead Box O Transcription Factor Axis Regulates Human Cytomegalovirus Replication.Akt 叉头框 O 转录因子轴调节人巨细胞病毒复制。
mBio. 2022 Aug 30;13(4):e0104222. doi: 10.1128/mbio.01042-22. Epub 2022 Aug 10.
10
Activation of creER recombinase in the mouse calvaria induces local recombination without effects on distant skeletal segments.在小鼠颅骨中激活 creER 重组酶会诱导局部重组，而不会对远处的骨骼节段产生影响。
Sci Rep. 2021 Apr 15;11(1):8214. doi: 10.1038/s41598-021-87611-2.
本文引用的文献
1
Tamoxifen administration to mice.对小鼠给予他莫昔芬。
Cold Spring Harb Protoc. 2015 Mar 2;2015(3):269-71. doi: 10.1101/pdb.prot077966.
2
Validation of MdmX as a therapeutic target for reactivating p53 in tumors.验证 MdmX 作为肿瘤中重新激活 p53 的治疗靶点。
Genes Dev. 2011 Aug 15;25(16):1746-57. doi: 10.1101/gad.16722111.
3
Selective activation of p53-mediated tumour suppression in high-grade tumours.选择性激活 p53 介导的高级别肿瘤中的肿瘤抑制作用。
Nature. 2010 Nov 25;468(7323):567-71. doi: 10.1038/nature09526.
4
Fulvestrant - a novel endocrine therapy for breast cancer.氟维司群——一种新型乳腺癌内分泌治疗药物。
Curr Med Chem. 2010;17(10):902-14. doi: 10.2174/092986710790820633.
5
A tamoxifen inducible knock-in allele for investigation of E2A function.用于研究E2A功能的他莫昔芬诱导型敲入等位基因。
BMC Dev Biol. 2009 Oct 12;9:51. doi: 10.1186/1471-213X-9-51.
6
Distinct thresholds govern Myc's biological output in vivo.不同的阈值在体内调控Myc的生物学效应。
Cancer Cell. 2008 Dec 9;14(6):447-57. doi: 10.1016/j.ccr.2008.10.018.
7
Generation of a transgenic mouse model with chondrocyte-specific and tamoxifen-inducible expression of Cre recombinase.构建一种具有软骨细胞特异性且可通过他莫昔芬诱导表达Cre重组酶的转基因小鼠模型。
Genesis. 2007 Jan;45(1):44-50. doi: 10.1002/dvg.20261.
8
Modeling the therapeutic efficacy of p53 restoration in tumors.模拟p53恢复在肿瘤中的治疗效果。
Cell. 2006 Dec 29;127(7):1323-34. doi: 10.1016/j.cell.2006.12.007. Epub 2006 Dec 21.
9
Mdm2 is critically and continuously required to suppress lethal p53 activity in vivo.Mdm2对于在体内抑制致死性的p53活性至关重要且持续发挥作用。
Cancer Cell. 2006 Dec;10(6):501-14. doi: 10.1016/j.ccr.2006.10.010.
10
VE-cadherin-CreERT2 transgenic mouse: a model for inducible recombination in the endothelium.血管内皮钙黏蛋白-CreERT2转基因小鼠：一种用于内皮细胞诱导性重组的模型。
Dev Dyn. 2006 Dec;235(12):3413-22. doi: 10.1002/dvdy.20982.
Zotero 插件