一种新型的小鼠Cre驱动系,靶向新生小鼠肺中表达脂滴包被蛋白2的细胞。
A novel mouse Cre-driver line targeting Perilipin 2-expressing cells in the neonatal lung.
作者信息
Ntokou Aglaia, Szibor Marten, Rodríguez-Castillo José Alberto, Quantius Jennifer, Herold Susanne, El Agha Elie, Bellusci Saverio, Salwig Isabelle, Braun Thomas, Voswinckel Robert, Seeger Werner, Morty Rory E, Ahlbrecht Katrin
机构信息
Department of Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, member of the German Center for Lung Research (DZL), Bad Nauheim, Germany.
Department of Internal Medicine (Pulmonology), Universities of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany.
出版信息
Genesis. 2017 Dec;55(12). doi: 10.1002/dvg.23080. Epub 2017 Oct 27.
Pulmonary diseases such as chronic obstructive pulmonary disease, lung fibrosis, and bronchopulmonary dysplasia are characterized by the destruction or malformation of the alveolar regions of the lung. The underlying pathomechanisms at play are an area of intense interest since these mechanisms may reveal pathways suitable for interventions to drive reparative processes. Lipid-laden fibroblasts (lipofibroblasts) express the Perilipin 2 (Plin2) gene-product, PLIN2, commonly called adipose-differentiation related protein (ADRP). These cells are also thought to play a role in alveolarization and repair after injury to the alveolus. Progress in defining the functional contribution of lipofibroblasts to alveolar generation and repair is hampered by a lack of in vivo tools. The present study reports the generation of an inducible mouse Cre-driver line to target cells of the ADRP lineage. Robust Cre-mediated recombination in this mouse line was detected in mesenchymal cells of the postnatal lung, and in additional organs including the heart, liver, and spleen. The generation and validation of this valuable new tool to genetically target, manipulate, and trace cells of the ADRP lineage is critical for assessing the functional contribution of lipofibroblasts to lung development and repair.
诸如慢性阻塞性肺疾病、肺纤维化和支气管肺发育不良等肺部疾病的特征是肺的肺泡区域遭到破坏或出现畸形。由于这些机制可能揭示出适合干预以推动修复过程的途径,因此其潜在的病理机制是一个备受关注的领域。富含脂质的成纤维细胞(脂成纤维细胞)表达 perilipin 2(Plin2)基因产物 PLIN2,通常称为脂肪分化相关蛋白(ADRP)。这些细胞也被认为在肺泡损伤后的肺泡化和修复过程中发挥作用。由于缺乏体内工具,确定脂成纤维细胞对肺泡生成和修复的功能贡献方面的进展受到阻碍。本研究报告了一种可诱导的小鼠 Cre 驱动系的产生,用于靶向 ADRP 谱系的细胞。在该小鼠品系中,在出生后肺的间充质细胞以及包括心脏、肝脏和脾脏在内的其他器官中检测到了强大的 Cre 介导的重组。这种用于对 ADRP 谱系细胞进行基因靶向、操纵和追踪的有价值的新工具的产生和验证,对于评估脂成纤维细胞对肺发育和修复的功能贡献至关重要。