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荧光 perilipin 2 敲入小鼠模型揭示了在发育中和成年脑中存在大量的脂滴。

A fluorescent perilipin 2 knock-in mouse model reveals a high abundance of lipid droplets in the developing and adult brain.

机构信息

Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.

Biozentrum, University of Basel, Basel, Switzerland.

出版信息

Nat Commun. 2024 Jun 28;15(1):5489. doi: 10.1038/s41467-024-49449-w.

Abstract

Lipid droplets (LDs) are dynamic lipid storage organelles. They are tightly linked to metabolism and can exert protective functions, making them important players in health and disease. Most LD studies in vivo rely on staining methods, providing only a snapshot. We therefore developed a LD-reporter mouse by labelling the endogenous LD coat protein perilipin 2 (PLIN2) with tdTomato, enabling staining-free fluorescent LD visualisation in living and fixed tissues and cells. Here we validate this model under standard and high-fat diet conditions and demonstrate that LDs are highly abundant in various cell types in the healthy brain, including neurons, astrocytes, ependymal cells, neural stem/progenitor cells and microglia. Furthermore, we also show that LDs are abundant during brain development and can be visualized using live imaging of embryonic slices. Taken together, our tdTom-Plin2 mouse serves as a novel tool to study LDs and their dynamics under both physiological and diseased conditions in all tissues expressing Plin2.

摘要

脂滴(LDs)是动态的脂质储存细胞器。它们与代谢紧密相关,并能发挥保护功能,因此在健康和疾病中起着重要作用。体内大多数 LD 研究依赖于染色方法,只能提供一个快照。因此,我们通过标记内源性 LD 外壳蛋白 perilipin 2(PLIN2)来开发 LD 报告小鼠,从而能够在活体和固定组织和细胞中进行无染色的荧光 LD 可视化。在这里,我们在标准和高脂肪饮食条件下验证了该模型,并证明了 LD 在健康大脑中的各种细胞类型中非常丰富,包括神经元、星形胶质细胞、室管膜细胞、神经干细胞/祖细胞和小胶质细胞。此外,我们还表明,在大脑发育过程中 LD 也很丰富,并且可以使用胚胎切片的活体成像来观察。总之,我们的 tdTom-Plin2 小鼠是一种新的工具,可以在所有表达 Plin2 的组织中研究生理和疾病条件下的 LD 及其动态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/450c/11213871/64ff53d48b80/41467_2024_49449_Fig1_HTML.jpg

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