Adriamycin produces a reproducible teratogenic model of vertebral, anal, cardiovascular, tracheal, esophageal, renal, and limb anomalies in the mouse
Adriamycin produces a reproducible teratogenic model of vertebral, anal, cardiovascular, tracheal, esophageal, renal, and limb anomalies in the mouse
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DOI：
10.1016/j.jpedsurg.2007.05.018
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发表时间：
2007-10-01
影响因子：
2.4
通讯作者：
Puri, Prem
中科院分区：
文献类型：
--
作者：
Dawrant, Michael J.;Giles, Shay;Puri, Prem
背景/目的：阿霉素大鼠模型是脊椎、肛门、心脏、气管、食管、肾脏和肢体（VEGIL）异常和胃肠道闭锁的已建立模型。小鼠是发育生物学家研究的最重要的哺乳动物，为转基因研究提供了更多的分子探针，抗体和可转移的知识。先前在阿霉素小鼠模型中仅描述了气管食管畸形。本研究的目的是进行一个剂量反应分析的致畸性阿霉素在小鼠中，以确定影响的剂量和暴露时间在生产气管食管畸形，并显示它是否会导致其他VEGYL anomals.Methods：CBA/Ca小鼠准确的时间交配（n = 30）。四种不同剂量（0 [盐水]、4、5和6 mg/kg）的阿霉素（EBEWE Pharma Ges.m.b.H. Nfg。KG，A-4866 Unterach，Austria）在3个不同的注射时间进行比较。母鼠接受2次腹膜内注射，间隔24小时，从第7、7.5或8天开始。在第18天收获胎仔。使用解剖显微镜和连续横切片检查异常。结果：在第7天和第8天给予6 mg/kg阿霉素具有最大的致畸作用，80%的胎儿具有3个或更多VEGF-L异常：肛门直肠畸形，100%;气管食管畸形，50%;右侧主动脉弓，58.3%;膀胱发育不全/双侧肾盂积水，100%。这项研究建立了一个小鼠模型，应该提供深入了解的细胞和分子机制的VEGIL异常。(C)2007年爱思唯尔公司All rights reserved.
Background/Purpose: The Adriamycin rat model is an established model for vertebral, anal, cardiac, tracheal, esophageal, renal, and limb (VACTERL) anomalies and gastrointestinal atresias. Mice are the foremost mammal studied by developmental biologists, providing greater availability of molecular probes, antibodies, and transferable knowledge with transgenic studies. Only tracheoesophageal malformations have been previously described in the Adriamycin mouse model. The aim of this study was to carry out a dose-response analysis of the teratogenicity of Adriamycin in the mouse to determine the effect of the dose and timing of exposure in producing tracheoesophageal malformations and show if it causes other VACTERL anomalies.Methods: CBA/Ca mice were accurately time mated (n = 30). Four different doses (0 [saline], 4, 5, and 6 mg/kg) of Adriamycin (EBEWE Pharma Ges.m.b.H. Nfg. KG, A-4866 Unterach, Austria) at 3 different timings of injections were compared. Dams received 2 intraperitoneal injections, 24 hours apart, commencing on day 7, 7.5, or 8. Fetuses were harvested on day 18. Anomalies were examined using a dissecting microscope and serial transverse sections.Results: Administering Adriamycin at 6 mg/kg on days 7 and 8 had the most teratogenic effect, with 80% of fetuses having 3 or more VACTER-L anomalies: anorectal malformation, 100%; tracheoesophageal malformation, 50%; right-sided aortic arch, 58.3%; bladder agenesis/bilateral hydronephrosis, 100%.Conclusion: This study establishes a mouse model that should provide insights into the cellular and molecular mechanisms underlying VACTERL anomalies. (C) 2007 Elsevier Inc. All rights reserved.