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小鼠中FAM19A5部分缺陷会导致脊柱成熟受阻、多动以及恐惧反应改变。

Partial FAM19A5 deficiency in mice leads to disrupted spine maturation, hyperactivity, and an altered fear response.

作者信息

Shahapal Anu, Park Sumi, Yoo Sangjin, Ma Shi-Xun, Lee Jongha, Kwak Hoyun, Hwang Jong-Ik, Seong Jae Young

机构信息

Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seoul, Republic of Korea.

Neuracle Science Co., Ltd., Seoul, Republic of Korea.

出版信息

PLoS One. 2025 Aug 5;20(8):e0327493. doi: 10.1371/journal.pone.0327493. eCollection 2025.

DOI:10.1371/journal.pone.0327493
PMID:40763294
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12324117/
Abstract

The FAM19A5 polypeptide, encoded by the TAFA5 gene, is evolutionarily conserved among vertebral species. This protein is predominantly expressed in the brain, highlighting its crucial role in the central nervous system. Here, we investigated the potential roles of FAM19A5 in brain development and behavior using a FAM19A5-LacZ KI mouse model. This model exhibited a partial reduction in the FAM19A5 protein level. FAM19A5-LacZ KI mice displayed no significant alterations in gross brain structure but alterations in dendritic spine distribution, with a bias toward immature forms. These mice also had lower body weights. Behavioral tests revealed that compared with their wild-type littermates, FAM19A5-LacZ KI male mice displayed hyperactivity and a delayed innate fear response. These findings suggest that FAM19A5 plays a role in regulating spine maturation and maintenance, thereby contributing to neural connectivity and behavior.

摘要

由TAFA5基因编码的FAM19A5多肽在脊椎动物物种中具有进化保守性。这种蛋白质主要在大脑中表达,突显了其在中枢神经系统中的关键作用。在此,我们使用FAM19A5-LacZ基因敲入小鼠模型研究了FAM19A5在大脑发育和行为中的潜在作用。该模型显示FAM19A5蛋白水平部分降低。FAM19A5-LacZ基因敲入小鼠整体大脑结构未显示出显著改变,但树突棘分布发生了变化,倾向于未成熟形式。这些小鼠体重也较低。行为测试表明,与野生型同窝小鼠相比,FAM19A5-LacZ基因敲入雄性小鼠表现出多动和先天恐惧反应延迟。这些发现表明,FAM19A5在调节脊柱成熟和维持中发挥作用,从而有助于神经连接和行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da10/12324117/0fe297fd034a/pone.0327493.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da10/12324117/0b85dd166d19/pone.0327493.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da10/12324117/08b6a4d68a55/pone.0327493.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da10/12324117/629ed173ca75/pone.0327493.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da10/12324117/25d277b356ec/pone.0327493.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da10/12324117/6597eaa57bb3/pone.0327493.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da10/12324117/4c511c4d8586/pone.0327493.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da10/12324117/0fe297fd034a/pone.0327493.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da10/12324117/0b85dd166d19/pone.0327493.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da10/12324117/08b6a4d68a55/pone.0327493.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da10/12324117/629ed173ca75/pone.0327493.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da10/12324117/25d277b356ec/pone.0327493.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da10/12324117/6597eaa57bb3/pone.0327493.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da10/12324117/4c511c4d8586/pone.0327493.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da10/12324117/0fe297fd034a/pone.0327493.g007.jpg

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本文引用的文献

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Is FAM19A5 an adipokine? Peripheral FAM19A5 in wild-type, FAM19A5 knockout, and LacZ knockin mice.FAM19A5是一种脂肪因子吗?野生型、FAM19A5基因敲除型和LacZ基因敲入型小鼠的外周FAM19A5 。
Mol Cells. 2024 Dec;47(12):100125. doi: 10.1016/j.mocell.2024.100125. Epub 2024 Oct 18.
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FAM19A5 Deficiency Mitigates the Aβ Plaque Burden and Improves Cognition in Mouse Models of Alzheimer's Disease.FAM19A5基因缺陷减轻阿尔茨海默病小鼠模型中的Aβ斑块负担并改善认知功能。
Exp Neurobiol. 2024 Aug 31;33(4):193-201. doi: 10.5607/en24017.
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Primary somatosensory cortex bidirectionally modulates sensory gain and nociceptive behavior in a layer-specific manner.
初级躯体感觉皮层以特定于层的方式双向调节感觉增益和伤害感受行为。
Nat Commun. 2023 May 24;14(1):2999. doi: 10.1038/s41467-023-38798-7.
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Comparison of Golgi-Cox and Intracellular Loading of Lucifer Yellow for Dendritic Spine Density and Morphology Analysis in the Mouse Brain.高尔基染色和 Lucifer Yellow 内染法在分析小鼠脑内树突棘密度和形态中的比较。
Neuroscience. 2022 Aug 21;498:1-18. doi: 10.1016/j.neuroscience.2022.06.029. Epub 2022 Jun 23.
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Deorphanizing FAM19A proteins as pan-neurexin ligands with an unusual biosynthetic binding mechanism.将 FAM19A 蛋白去孤儿化为泛神经连接蛋白配体,具有不寻常的生物合成结合机制。
J Cell Biol. 2020 Sep 7;219(9). doi: 10.1083/jcb.202004164.
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Up and Down States and Memory Consolidation Across Somatosensory, Entorhinal, and Hippocampal Cortices.体感皮层、内嗅皮层和海马体皮层中的兴奋和抑制状态与记忆巩固
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