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正常成年海马神经发生在 SRG3 过表达转基因小鼠中。

Normal Adult Hippocampal Neurogenesis in SRG3-overexpressing Transgenic Mice.

机构信息

Department of Biochemistry and Molecular Biology, Hanyang University College of Medicine, Seoul 133-791, Korea.

出版信息

Exp Neurobiol. 2010 Jun;19(1):39-48. doi: 10.5607/en.2010.19.1.39. Epub 2010 Jun 30.

DOI:10.5607/en.2010.19.1.39
PMID:22110340
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3214793/
Abstract

SRG3 (SWI3-related gene) is a core subunit of mouse SWI/SNF complex and is known to play a critical role in stabilizing the SWI/SNF complex by attenuating its proteasomal degradation. SWI/SNF chromatin remodeling complex is reported to act as an important endogenous regulator in the proliferation and differentiation of mammalian neural stem cells. Because limited expression of SRG3 occurs in the brain and thymus during mouse embryogenesis, it was hypothesized that the altered SRG3 expression level might affect the process of adult hippocampal neurogenesis. Due to the embryonic lethality of homozygous knockout mice, this study focuses on dissecting the effect of overexpressed SRG3 on adult hippocampal neurogenesis. The BrdU incorporation assay, immunostaing with neuronal markers for each differentiation stage, and imunoblotting analysis with intracellular molecules involved in survival in adult hippocampal neurogenesis found no alteration, suggesting that the overexpression of SRG3 protein in mature neurons had no effect on the entire process of adult hippocampal neurogenesis including proliferation, differentiation, and survival.

摘要

SRG3（SWI3 相关基因）是小鼠 SWI/SNF 复合物的核心亚基，已知通过减弱其蛋白酶体降解来稳定 SWI/SNF 复合物。报道称，SWI/SNF 染色质重塑复合物在哺乳动物神经干细胞的增殖和分化中起重要的内源性调节作用。由于在小鼠胚胎发生过程中，SRG3 在大脑和胸腺中的表达有限，因此假设改变的 SRG3 表达水平可能会影响成年海马神经发生的过程。由于纯合敲除小鼠的胚胎致死性，本研究重点在于剖析过表达 SRG3 对成年海马神经发生的影响。BrdU 掺入测定、各分化阶段的神经元标志物免疫染色和涉及成年海马神经发生中存活的细胞内分子的免疫印迹分析均未发现改变，表明成熟神经元中 SRG3 蛋白的过表达对包括增殖、分化和存活在内的整个成年海马神经发生过程没有影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5264/3214793/b85cdbd5c0c1/en-19-39-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5264/3214793/4edda5f4da87/en-19-39-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5264/3214793/e0de02bb62bb/en-19-39-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5264/3214793/0bc2b173cf56/en-19-39-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5264/3214793/b3d426ee2904/en-19-39-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5264/3214793/b85cdbd5c0c1/en-19-39-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5264/3214793/4edda5f4da87/en-19-39-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5264/3214793/e0de02bb62bb/en-19-39-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5264/3214793/0bc2b173cf56/en-19-39-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5264/3214793/b3d426ee2904/en-19-39-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5264/3214793/b85cdbd5c0c1/en-19-39-g005.jpg

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本文引用的文献

1
Mechanisms and functional implications of adult neurogenesis.成体神经发生的机制及其功能意义。
Cell. 2008 Feb 22;132(4):645-60. doi: 10.1016/j.cell.2008.01.033.
2
SRG3, a core component of mouse SWI/SNF complex, is essential for extra-embryonic vascular development.SRG3是小鼠SWI/SNF复合物的核心组成部分，对胚胎外血管发育至关重要。
Dev Biol. 2008 Mar 1;315(1):136-46. doi: 10.1016/j.ydbio.2007.12.024. Epub 2007 Dec 27.
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Neurogenesis in the adult hippocampus.成年海马体中的神经发生。
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Creating a neurogenic environment: the role of BDNF and FGF2.创造神经源性环境：脑源性神经营养因子和碱性成纤维细胞生长因子的作用。
Mol Cell Neurosci. 2007 Sep;36(1):108-20. doi: 10.1016/j.mcn.2007.06.004. Epub 2007 Jul 4.
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An essential switch in subunit composition of a chromatin remodeling complex during neural development.神经发育过程中染色质重塑复合物亚基组成的关键转变。
Neuron. 2007 Jul 19;55(2):201-15. doi: 10.1016/j.neuron.2007.06.019.
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How widespread is adult neurogenesis in mammals?成年哺乳动物的神经发生有多普遍？
Nat Rev Neurosci. 2007 Jun;8(6):481-8. doi: 10.1038/nrn2147.
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Experience-specific functional modification of the dentate gyrus through adult neurogenesis: a critical period during an immature stage.通过成体神经发生实现齿状回的经验特异性功能修饰：未成熟阶段的关键时期。
J Neurosci. 2007 Mar 21;27(12):3252-9. doi: 10.1523/JNEUROSCI.4941-06.2007.
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SRG3 interacts directly with the major components of the SWI/SNF chromatin remodeling complex and protects them from proteasomal degradation.SRG3直接与SWI/SNF染色质重塑复合体的主要成分相互作用，并保护它们免受蛋白酶体降解。
J Biol Chem. 2007 Apr 6;282(14):10614-24. doi: 10.1074/jbc.M610563200. Epub 2007 Jan 24.
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Changes in microtubule-associated protein-2 (MAP2) expression during development and after status epilepticus in the immature rat hippocampus.未成熟大鼠海马体发育过程中及癫痫持续状态后微管相关蛋白2（MAP2）表达的变化
Int J Dev Neurosci. 2007 Apr;25(2):121-31. doi: 10.1016/j.ijdevneu.2006.12.001. Epub 2006 Dec 20.
10
Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation.成年海马神经发生中与双皮质素相关的树突成熟的变异性独立于前体细胞增殖的调节。
BMC Neurosci. 2006 Nov 15;7:77. doi: 10.1186/1471-2202-7-77.