Name: a novel surgical approach for intratracheal administration of bioactive agents in a fetal mouse model
Uploaded: 2012-10-31T13:00:00
Description: Watch this Scientific Journal Video about A Novel Surgical Approach for Intratracheal Administration of Bioactive Agents in a Fetal Mouse Model at JoVE.com

，MC和AVDP是支持的博士后研究员在佛兰德（IWT-佛兰德），通过科学和技术创新促进研究所的补助金。 JT持有的一部分的时间临床研究奖学金（KOOR，）UZ Leuven的。 DV是一个博士后研究员，鲁汶大学的资助，DBOF/10/062的支持。 MMdC是一个博士后研究员，从Conselho国家PesquisaËDesenvolvimento（CNPq）和伊拉斯谟的赠款支持。研究是由IWT-佛兰德，由欧共体授予DIMI的（LSHB-CT-2005-512146）和体内分子成像研究组（IMIR）的鲁汶大学。我们要感谢詹姆斯·M·威尔逊创办的宾夕法尼亚大学矢量核心，他们的AAV6.2包装质粒的腺相关病毒载体生产的一种礼物。

1。小鼠交配，以获得所需的妊娠阶段时间交配怀孕NMRI小鼠，使他们怀孕18天（E18）（总妊娠E19.5）的手术时间。前和手术后他们被安置在过滤器顶部笼，免费使用水和周星驰在正常的室温和正常的日光。 2。 （IT）胎儿气管内注射（图1） <ol><li>首先提交怀孕NMRI小鼠全身麻醉与异氟醚1.5％O 2的混合物在1.5 L / min的。的异氟醚的水平取决于年龄和应?...

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关键步骤<ul><li>小鼠品系，我们选择了与NMRI小鼠，因为他们有丰富的幼崽（平均窝产仔数14.4±1.8，自己的数据），以及容忍的干预，并具有良好的母体特征。 </li><li>通过子宫壁和胎膜配售的钱袋是关键的一步，因为你只是想揭露胎儿的头和肩膀，否则重新定位，几乎是不可能的，而不会造成创伤。 </li><li>胎儿的头向后伸展的最佳位置正上方的气管切开是必要的，以这样可以避免大血管（颈静脉?...

<table border="1"><tbody><tr><td> 的试剂的名称 </td><td> 公司 </td><td> 目录编号 </td><td> 评论（可选） </td></tr><tr><td> NMRI小鼠</td><td>让维耶，乐圣岛，法国Genest </td><td></td><td></td></tr><tr><td>异氟醚</td><td> Isoba，英特威/先灵葆雅动物保健，米尔顿凯恩斯，英国</td><td></td><td></td></tr><tr><td>普理灵6-0 </td><td>爱惜，比利时，格罗特北臼阿登</td><td></td><td></td></tr><tr><td>薇乔5-0 </td><td>爱惜，比利时，格罗特北臼阿登</td><td></td><td></td></tr><tr><td> 50微升的汉密尔顿玻璃注射器，型号1710.5 TLLX SYR </td><td>汉密尔顿，雷诺，内华达州，美国</td><td> 5495-20 </td><td></td></tr><tr><td> 30G针</td><td>汉密尔顿，雷诺，内华达州，美国</td><td> 7762-03 </td><td></td></tr><tr><td> 2％利多卡因</td><td>阿斯利康（AstraZeneca），荷兰Zoetermeer </td><td></td><td></td></tr></tbody></table>

a novel surgical approach for intratracheal administration of bioactive agents in a fetal mouse model

产前肺部给药的细胞，基因或药物制剂可以提供各种遗传性和获得性疾病的新的治疗策略的基础。除了从先天性或继承异常要求交付的基因，几个非继承围产期条件，其中短期基因表达或药理干预是足以达到治疗效果的长期表达，被认为是作为潜在的未来的适应症种方法。候选短期产前治疗疾病的应用可能是的暂时性新生儿缺陷的表面活性蛋白B引起新生儿呼吸窘迫综合征1,2或高氧损伤的新生儿肺3。永久的治疗矫正的候选疾病囊性纤维化（CF）4，表面活性剂的不足5和α1-抗胰蛋白酶缺乏症的遗传变异。 &lt;P类=“j​​ove_content”&gt;一般情况下，产前基因治疗的一个重要优势是能够开始在开发的早期治疗干预，甚至是在病人的临床表现之前，从而防止个人造成不可弥补的损害。此外，胎儿各器官的细胞增殖率增加相比，成人的器官，它可以让一个更有效的基因或干细胞进入胎儿体内转移。此外， 在子宫内的基因传递的个体的免疫系统时，进行不完全成熟。因此，异源细胞的移植或补充的非功能性的或缺失的蛋白质与一个正确的版本应该不会引起免疫致敏的细胞，载体或转基因产物，它最近已被证明是细胞和基因疗法的情况下，7 。 在本研究中，我们调查的潜在直接定位在小鼠胎儿的气管米ODEL。本程序是在使用在大型动物模型中，如兔，羊8，即使在临床的设置9，但迄今尚未在小鼠模型中之前进行。在研究潜在的胎儿基因治疗遗传性疾病，如CF，作为第一个证明了的概念，因为不同的转基因小鼠品系中，有据可查的胚胎发育和胎儿的发育，不那么严格的广泛使用的小鼠模型是非常有用的伦理规范，妊娠期短及大窝产仔数。 已经描述了不同的访问路线针对的胎儿鼠肺，包括羊膜腔内注射10-12，（超声引导）肺内注射13,14和静脉内给药到卵黄囊船只15,16或脐静脉17。我们的新型外科手术使研究人员能够直接注射剂的选择，允许进入胎儿小鼠气管为更有效地提供比现有技术18呼吸道。

Watch this Scientific Journal Video about A Novel Surgical Approach for Intratracheal Administration of Bioactive Agents in a Fetal Mouse Model at JoVE.com

A Novel Surgical Approach for Intratracheal Administration of Bioactive Agents in a Fetal Mouse Model

我们开发了一种新的手术方法气管内给药的生物活性剂的胎鼠。运送路线是更有效地针对胎儿比常用的羊膜腔内注射的小鼠肺组织。这个过程至今没有在小鼠模型中被描述。

一种新的手术方法气管内注射生物活性剂在胎鼠模型

Prenatal pulmonary delivery of cells, genes or pharmacologic agents could provide the basis for new therapeutic strategies for a variety of genetic and ...

Research

JoVE Journal

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在斑马鱼模型的胎儿酒精暴露评估致畸的变化

Fetal alcohol syndrome (FAS) is a severe manifestation of embryonic exposure to ethanol. It presents with characteristic defects to the face and organs, ...

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Investigators have utilized a wide array of animal models and investigative techniques to study the mammalian auditory system. Much of the basic research ...

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Surgical Approach for Middle Cerebral Artery Occlusion and Reperfusion Induced Stroke in Mice

对大脑中动脉闭塞再灌注损伤诱发中风小鼠的手术方法

Stroke is a leading cause of death worldwide and continues to be one of the major causes of long-term adult disabilities. About 87% of strokes are ...

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应急方案和设置药物和液体管理的新方法

The available routes of administration commonly used for medications and fluids in the acute care setting are generally limited to oral, intravenous, or ...

Use of a Central Venous Line for Fluids, Drugs and Nutrient Administration in a Mouse Model of Critical Illness

在重大疾病的小鼠模型中使用中心静脉导管的流体，药物和营养管理

This protocol describes a centrally catheterized mouse model of prolonged critical illness. We combine the cecal ligation and puncture method to induce ...

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A Rat Model of Orthotopic Liver Transplantation Using a Novel Magnetic Anastomosis Technique for Suprahepatic Vena Cava Reconstruction

应用新型磁吻合技术 Suprahepatic 腔静脉重建大鼠原位肝移植模型的研究

The rat model of orthotopic liver transplantation (OLT) is essential for transplant research. It is a very sophisticated animal model and requires a steep ...