Name: assessing functional performance in the mdx mouse model
Uploaded: 2014-03-27T21:45:00
Description: Watch this Scientific Journal Video about Assessing Functional Performance in the Mdx Mouse Model at JoVE.com

我们要感谢玛格丽特Hulsker为她照相援助和获得小鼠的图像和审稿人非常有建设性的意见帮助。这项工作是由ZonMw，TREAT-NMD（合同号利星行-CT-2006-036825）和杜氏父项目的支持。

这里所描述的实验是批准莱顿大学医学中心（LUMC）的动物伦理委员会（DEC）。小鼠经LUMC的动物饲养设施，并保持在单独通风笼12小时光线暗周期。他们有自由采食饮水和标准饲料。 当执行任何下文所述的功能测试，实验条件必须严格控制，以减少偏差。最好是，年龄和性别匹配的老鼠应该使用，年龄和性别之间的性能差异。属于同窝小鼠应该随机对实验组。动物应该?...

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Genome. 11, 725-728 (2000).</li><li>Chapillon, P., Lalonde, R., Jones, N., Caston, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Early+development+of+synchronized+walking+on+the+rotorod+in+rats.+Effects+of+training+and+handling.">Early development of synchronized walking on the rotorod in rats. Effects of training and handling.</a> Behav. Brain Res. 93, 77-81 (1998).</li><li>Massett, M. P., Berk, B. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Strain-dependent+differences+in+responses+to+exercise+training+in+inbred+and+hybrid+mice.">Strain-dependent differences in responses to exercise training in inbred and hybrid mice.</a> Am. J. Physiol. Regul. Integr. Comp. Physiol. 288, 1006-1013 (2005).</li><li>Lerman, I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genetic+variability+in+forced+and+voluntary+endurance+exercise+performance+in+seven+inbred+mouse+strains.">Genetic variability in forced and voluntary endurance exercise performance in seven inbred mouse strains.</a> J. Appl. Physiol. 92, 2245-2255 (2002).</li><li>Sharp, P. S., Jee, H., Wells, D. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Physiological+characterization+of+muscle+strength+with+variable+levels+of+dystrophin+restoration+in+mdx+mice+following+local+antisense+therapy.">Physiological characterization of muscle strength with variable levels of dystrophin restoration in mdx mice following local antisense therapy.</a> Mol. Ther. 19, 165-171 (2011).</li><li>Klein, S. 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这里介绍的功能测试是可重复的，易于实施，并适用于野生型和独立的年龄的营养不良小鼠。该测试提供有用的工具，临床前评估肌肉功能，强度，条件和协调。当测试的化合物对疾病的自然史的影响，非侵入性的试验方法如下所述（前肢握力，这两个挂试验和旋转试验）可以很好地结合在这些测试是在连续数天进行功能测试制度。这些协议是不损害mdx小鼠，并且可以在纵向方式10...

假肥大型肌营养不良症（DMD）是最常见的神经肌肉疾病影响1:5,000新生男婴。这个严重的和渐进性肌肉萎缩病是由在DMD基因的突变，破坏开放读码框，并防止功能性肌养蛋白的合成所引起。肌纤维缺乏抗肌萎缩蛋白很容易受到运动性损伤。因肌肉的再生能力耗尽，并且由于受损的肌肉的慢性炎症，纤维由结缔组织和脂肪替代，随​​后导致功能丧失。一般情况下，DMD患者失去在第二个十年早期下肢行走。后来，又在胳膊和肩胛带肌肉受到影响，患者往往发展胸腰段脊柱侧凸，由于配套的脊髓肌肉不对称弱化。辅助通气，通常需要在晚十几岁或二十出头。呼吸和心脏衰竭铅死在第三或第四个十年1。 虽然致病基因已被发现在25年前2，没有可用于DMD的治疗。然而，改善医疗保健和使用糖皮质激素已在西方世界3提高寿命。通过使用像mdx小鼠的动物模型，主要步骤迈进的潜在治疗策略的发现已经作出。 mdx小鼠是最常用的DMD小鼠模型。它在小鼠DMD基因的外显子23点突变，因而缺乏抗肌萎缩蛋白4。在过去的几年中，许多建议策略已进展到临床试验5-9。在这些试验中，改善肌肉功能是主要终点，相关测试期间的前临床阶段测试化合物对肌肉功能的好处在小鼠中的重要性。 像DMD患者，也mdx小鼠的抗肌萎缩蛋白阴性肌纤维很容易受到运动损伤和比较C57BL/10ScSnJ野生型小鼠的肌肉功能受损。这种损害可以具有多种功​​能性测试进行评估。这些测试是无创，不与肌肉病理（ 如前肢握力，挂测试和转棒运行）干扰。因此它们可用于监测疾病的自然史或确定化合物对疾病进展的影响。得到一个在化合物对mdx小鼠的肌肉功能的影响的深度图像，功能测试制度不与疾病进展，包括所有这些测试的干扰可以用于10。 可替换地，跑步机强制运行可用于故意加重疾病的发展和测试化合物11的保护能力。跑步机也可以是在运行时间，直到耗尽测量12，或作为一种工具，疲劳mdx小鼠，使它们在随后的功能测试，确保在性能上治疗组13之间较大的差异表现稍逊作为观察指标。当选择功能测试，他们对疾病进展的影响应该测试营养不良小鼠像mdx小鼠14特别是当牢记。 我们在这里详细描述了如何执行基于来自TREAT-NMD网络中可用的标准作业程序以可靠和可重复的方式是最常用的功能测试。 <a href="http://www.treat-nmd.eu/resources/research-resources/dmd-sops/" target="_blank">点击这里访问TREAT-NMD</a> 。

<table border="0" cellpadding="0" cellspacing="0" width="832">
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	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Mouse grip strength meter</td>
			<td style="width:331px;">Chatillon DFE (re-sold by Columbus Instruments)</td>
			<td style="width:119px;"># 80529</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Hanging wire 2 limbs device</td>
			<td style="width:331px;">Cloth hanger or custom made device</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Hanging wire 4 limbs device</td>
			<td style="width:331px;">Lid of rat cage or custom made device</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Rotarod</td>
			<td style="width:331px;">Ugo Basil</td>
			<td style="width:119px;"># 47600</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Treadmill for mice Exer 3/6</td>
			<td style="width:331px;">Columbus Instruments</td>
			<td style="width:119px;"># 1055SRM</td>
			<td></td>
		</tr>
	</tbody>
</table>

assessing functional performance in the mdx mouse model

假肥大型肌营养不良症（DMD）是一种严重和渐进性肌肉萎缩病也无法根治可用。然而，一些潜在的药物化合物和基因治疗方法已经进展到临床试验。随着改善肌肉功能是在这些试验中最重要的终点，很多重点放在了建立可靠，重现性好，易于进行功能测试，临床前评估肌肉功能，强度，条件，并在协调mdx小鼠模型的DMD。既侵袭性和非侵袭性测试可用。测试不恶化的疾病，可以用于确定疾病的自然史和治疗性干预（ 例如 ，前肢握力测试中，使用一个金属丝或栅和旋转杆运行两个不同的悬挂的测试）的影响。可替换地，跑步机强制运行可用于提高疾病进展和/或评估对疾病的病理治疗干预的保护作用。在这里，我们描述了如何在一个可靠和可重复的方式执行这些最常用的功能测试。使用这些协议基于标准作业程序使不同实验室之间的数据比较。

4-12周龄的野生型和mdx小鼠的前肢握力增加，再次降低了在老年小鼠。在力障碍已经可以在年轻的mdx小鼠进行观察。 9周龄的雌性小鼠的代表性数据示于图1A和 1B。虽然疲劳不菌株之间在这个年龄段有所不同的是，mdx小鼠比野生型小鼠弱。我们没有数据，但对疲劳性在旧的mdx和野生型小鼠。 获得可靠的和可重复的结果，多个评估需要由同...

Watch this Scientific Journal Video about Assessing Functional Performance in the Mdx Mouse Model at JoVE.com

Assessing Functional Performance in the Mdx Mouse Model

评估在功能性能<em&gt; MDX</em&gt;小鼠模型

在对神经肌肉疾病的临床试验的主要终点是普遍改善肌肉功能。因此，评估潜在的治疗化合物对肌肉性能在小鼠模型中的临床前的效果是非常重要的。我们在这里介绍几种功能测试，以解决这一问题。

Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder for which no cure is available. Nevertheless, several potential ...

Research

JoVE Journal

Behavior

Assessing Functional Performance in the Mdx Mouse Model

A Method for Investigating Age-related Differences in the Functional Connectivity of Cognitive Control Networks Associated with Dimensional Change Card Sort Performance

针对调查中的认知控制网络与关联维度变化卡片分类性能的功能连通性年龄相关性差异的方法

The ability to adjust behavior to sudden changes in the environment develops gradually in childhood and adolescence. For example, in the Dimensional ...

科研

行为学

The Emotional Stroop Task: Assessing Cognitive Performance under Exposure to Emotional Content

情绪Stroop任务：评估下暴露的认知表现的情感内容

The emotional Stroop effect (ESE) is the result of longer naming latencies to ink colors of emotion words than to ink colors of neutral words. The ...

The Rodent Psychomotor Vigilance Test (rPVT): A Method for Assessing Neurobehavioral Performance in Rats and Mice

The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice

鼠类精神运动警觉测试（rPVT）：一个在大鼠和小鼠的神经行为评估性能的方法

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article ...

Assessing Spatial Memory Impairment in a Mouse Model of Traumatic Brain Injury Using a Radial Water Tread Maze

使用径向水痕迷宫评估外伤性脑损伤小鼠模型中的空间记忆障碍

Despite the recent increase in use of mouse models in scientific research, researchers continue to use cognitive tasks that were originally designed and ...

Measuring Active and Passive Tameness Separately in Mice

小鼠主动和被动驯服的测定

Domesticated animals such as dogs and laboratory mice show a high level of tameness, which is important for humans to handle them easily. Tameness has two ...

Biomechanical Analysis Methods to Assess Professional Badminton Players' Lunge Performance

生物力学分析方法,以评估职业羽毛球运动员的隆起表现

Under the condition of simulating a badminton court in the laboratory, this study used the injury mechanism model to analyze the maximal right lunge ...

Assessing the Coherence of Parents' Short Narratives Regarding their Child Using the Five-Minute Speech Sample Procedure

使用五分钟言语样本程序评估家长对孩子的简短叙述的一致性

Valid and efficient measures for assessing the quality of parent-child relationships are needed to facilitate research and evidence-based practice with ...

A Task for Assessing the Impact of a Partner on the Speed and Accuracy of Motor Performance in Rats

评估合作伙伴对大鼠电机性能速度和准确性的影响的任务

To our knowledge, no study has examined the effect of mere presence on accuracy of performance in animals. Therefore, we developed an experimental task to ...

Training Dogs for Awake, Unrestrained Functional Magnetic Resonance Imaging

训练犬为觉醒，无节制的功能磁共振成像

We present a canine functional Magnetic Resonance Imaging (fMRI) training protocol that can be done in a cost-effective manner, with high-energy dogs, for ...

Human Circadian Phenotyping and Diurnal Performance Testing in the Real World

现实世界中的人类昼夜Phenotyping和二年性能测试

In our continuously developing &#39;around the clock&#39; society, there is a need to increase our understanding of how changes in biology, physiology and ...