Cell culture system to assay candidate genes and molecular pathways implicated in congenital diaphragmatic hernias.
Cell culture system to assay candidate genes and molecular pathways implicated in congenital diaphragmatic hernias.
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DOI：
10.1016/j.ydbio.2020.07.013
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发表时间：
2020-11-01
影响因子：
2.7
通讯作者：
Kardon G
中科院分区：
文献类型：
--
作者：
Bogenschutz EL;Sefton EM;Kardon G
哺乳动物的肌化横膈膜对于呼吸是必不可少的，并且发育中的横膈膜的缺陷导致常见且经常致命的出生缺陷，先天性膈疝（CDH）。人类遗传学研究表明，CDH涉及150多个基因和多个分子通路，但由于产生小鼠突变体的费用和时间，这些基因和分子通路中很少有被验证。胸膜腹膜皱襞（PPF）是膈肌发育过程中的暂时性胚胎结构，PPF的缺陷导致CDH。我们已经开发了一个系统，培养PPF成纤维细胞从E12.5小鼠胚胎，并表明，这些成纤维细胞，与常用的NIH 3T3成纤维细胞，保持在正常的膈肌发育的关键基因的表达。使用药理学和遗传操作，导致CDH在体内，我们还表明，在增殖的差异提供了一个快速的手段区分健康和受损的PPF成纤维细胞。因此，PPF成纤维细胞培养系统是一个有效的工具，用于检测CDH候选基因和分子通路的功能意义，并将是一个重要的资源，阐明复杂的病因CDH。
The mammalian muscularized diaphragm is essential for respiration and defects in the developing diaphragm cause a common and frequently lethal birth defect, congenital diaphragmatic hernia (CDH). Human genetic studies have implicated more than 150 genes and multiple molecular pathways in CDH, but few of these have been validated because of the expense and time to generate mouse mutants. The pleuroperitoneal folds (PPFs) are transient embryonic structures in diaphragm development and defects in PPFs lead to CDH. We have developed a system to culture PPF fibroblasts from E12.5 mouse embryos and show that these fibroblasts, in contrast to the commonly used NIH 3T3 fibroblasts, maintain expression of key genes in normal diaphragm development. Using pharmacological and genetic manipulations that result in CDH in vivo, we also demonstrate that differences in proliferation provide a rapid means of distinguishing healthy and impaired PPF fibroblasts. Thus, the PPF fibroblast cell culture system is an efficient tool for assaying the functional significance of CDH candidate genes and molecular pathways and will be an important resource for elucidating the complex etiology of CDH.
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DOI：
10.1002/bdra.20613
发表时间：
2010-01-01
影响因子：
--
作者：
Clugston, Robin D.;Zhang, Wei;Greer, John J.
通讯作者：
Greer, John J.
影响因子：
4.9
作者：
Farina, Nicholas H.;Hausburg, Melissa;Olwin, Bradley B.
通讯作者：
Olwin, Bradley B.
影响因子：
2
作者：
Arrington, Cammon B.;Bleyl, Steven B.;Matsunami, Nori;Bowles, Neil E.;Leppert, Tami I.;Demarest, Bradley L.;Osborne, Karen;Yoder, Bradley A.;Byrne, Janice L.;Schiffman, Joshua D.;Null, Donald M.;DiGeronimo, Robert;Rollins, Michael;Faix, Roger;Comstock, Jessica;Camp, Nicola J.;Leppert, Mark F.;Yost, H. Joseph;Brunelli, Luca
通讯作者：
Brunelli, Luca
影响因子：
1.8
作者：
Major, D;Cadenas, M;Cloutier, R
通讯作者：
Cloutier, R
影响因子：
4.5
作者：
COSTLOW, RD;MANSON, JM
通讯作者：
MANSON, JM