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。动物应该由同一运营商，谁是失明的实验组进行测试。测试应在白天和平日，同室的同时进行均衡的气味，噪音等个别小鼠和时间点之间14大变化可以用于所有被观察功能测试，因此6-8只/实验组应该被使用。功能测试性能也可以在很大程度上不同的近交系野生型菌株之间的差异。因此，实验组和对照野生型小鼠一定要有相应的背景（在mdx小鼠的使用C57BL/10ScSnJ野生型菌株）。这里描述的所有数据已取得与C57BL/10ScSnJ野生型菌株，其我们称之为野生型从这里开始。这里所描述的测试可以使用纵向从MDX和野生型小鼠至少1-19个月的年龄。测试不应该被重复超过每周一次，以防止老鼠失去兴趣和意愿来执行任务。 1。前肢握力测试使用前肢握力测试来测量前肢的强度。该测试是基于鼠标的倾向，本能地抓住一个网格时的尾巴15暂停，ADAPTEd从<a href="http://www.treat-nmd.eu/downloads/file/sops/dmd/MDX/dmd_m.2.2_001.pdf" target="_blank">DMD_M2.2.001.pdf</a> 。 <ol><li>设备设置：将一个网格，力传感器，测量拉过程中应用通过鼠标对电网的最大力量。确保设置是山顶上的张力模式（T-PK）的拉动。力的单位可以在任一盎司 - 力的，克 - 力的，磅力的，公斤 - 力的，或牛顿进行调整。 注意：我们喜欢与克为单位的值来工作。多种米市售，但只有轴向传感器给出可靠的结果为杠杆式力传感器是通过杠杆效应的物理规律负面影响。无论是nonflexible网格或三角形可用于棒是1-2毫米的直径。 </li><li>在测试之前，评估体重的鼠标，从而使归一化对于体重。 </li><li>用克为单位的值。重置仪表在每个RECO开始录制。 </li><li>通过抓住尾巴和水平移动对电网从笼中取出鼠标。 </li><li>检查鼠标掌握电网紧密地与两个前爪。 </li><li>拖动鼠标远离电网，以便其掌握被打破，适用于电网的最高力量将换能器的显示，它可以是手动或自动记录上显示。 </li><li>只需要拉考虑在鼠标显示抗实验者。拒绝，其中只有一个前爪或后肢中使用，并且其中鼠标拉过程中关措施。 </li><li>让鼠标拉格三次行，然后在笼子里返回它至少一分钟的休息期注：系列之间拉一个休息期是必要的鼠标恢复和避免习惯的形成。 </li><li>然后让鼠标执行四大系列拉，每个后跟一个短的休息时间。在这种方式的按钮鼠E有拉共15倍（3再换×5倍= 15拉）。 </li><li>确定最大握力和通过采取三个最高值的平均值出收集的15个值的归一化供体的重量。 </li><li>可选：通过计算前两个的平均值，最后两个系列拉1 +2 +3 = A，4 +5 +6 = B，10 +11 +12 = C和13 +14 +之间的递减确定疲劳15 = D。下式：（C + D）/（A + B）给出的1对小鼠不属于疲劳值。这可以用百分比来表示，使得鼠标不疲劳为0％的值和一个鼠标的前肢完全疲劳时具有100％的值。 </li></ol> 2。挂测试带悬挂试验，平衡，协调和肌肉状况进行评估。这些测试是基于小鼠都渴望继续挂在电线或网格，直到耗尽16的知识。有其中两个独特的悬挂试验在试验开始任只有两个前肢或四肢分别使用用金属丝或网格。使用线和网格挂试验是适于从最长的中止时间的方法<a href="http://www.treat-nmd.eu/downloads/file/sops/dmd/MDX/DMD_M.2.1.004.pdf" target="_blank">DMD_M.2.1.004.pdf</a>和<a href="http://www.treat-nmd.eu/downloads/file/sops/dmd/MDX/DMD_M.2.1.005.pdf" target="_blank">DMD_M.2.1.005.pdf</a>分别。用600秒的固定悬挂极限。大多数野生型小鼠的可以挂600秒，而营养不良的小鼠不能。以减少花费的时间进行该试验中，最大吊时间被设置到位。在此之前该脱落的线或网格小鼠给予长达两个多尝试。这样做是为了再保险，小鼠确实不能挂，不因笨拙下降。 <ol><li>吊试验与两肢<ol><li>设备设置：紧紧固定为2毫米厚的金属衣架用胶带架子和周围37保持架0;厘米上面有一层铺垫。注：另外，还可以使用55厘米，宽2mm厚的金属丝被紧紧地2纵看台之间的抵押。 37厘米的距离足以鼓励老鼠留挂，但也足够低，跌倒时防止老鼠从受伤。导线不应产生振动或在试验过程中置换出来，因为这可能会干扰小鼠的表现。 </li><li>通过尾部处理鼠标并把它的线附近。 </li><li>让鼠标抓住电线，只有两个前爪，及降低后肢在这样一种方式，鼠标只挂起与在电线上（ 图2B），这两个前爪。 </li><li>直接启动计时器，当鼠标被释放。释放后，强烈的小鼠试图抓住电线与所有的四肢和尾巴，这是允许的（ 图2C）。 </li><li>当鼠标显示了不恰当的行为（如平衡或故意跳下丝为SH拥有图2D和2E），直接通过更换鼠标的电线不停止计时器解决这个问题。 </li><li>当鼠标脱落的电线，停止计时并记录挂时间。 </li><li>当老鼠是能挂600秒，把他们赶走了电线，并将其返回到笼子里。在此之前限制落在老鼠都获得了最大两个的尝试。 </li><li>记录最大悬挂时间（ 即最长的试验），并使用它进行进一步的分析。 </li></ol></li><li>吊试验与四肢<ol><li>设备设置：使用一个手工制作的方形或一个大笼子里的老鼠或兔子本次测试的盖子。定位格25厘米以上柔软的被褥，以防止老鼠从坠落后伤害自己，而且要阻止小鼠故意跳下格。紧紧固定网格，使实验者不具备实验，这些运动过程中用手把握网格可能我nterfere用鼠标的性能。 </li><li>将鼠标放置在网格上，使其掌握它与它的四只爪子。 </li><li>颠倒的网格，使鼠标挂，直接启动定时器。 </li><li>测试会话结束的小鼠能够挂起600秒的持续时间。给予该脱落电网较早最多两个多尝试的小鼠。 </li><li>使用的最大吊时间（ 即 ，时间最长的试验）进行进一步分析。 </li></ol></li></ol> 3。旋转杆运行随着旋转试验的肌肉力量，协调，平衡和条件可确定17。 <ol><li>设备设置：对于此测试，小鼠必须在一个旋转管运行。确保稳定的速度设定为每分钟转速（rpm）5旋转，而当开始从5-45转在第15秒的速度增加。在此之后它具有保持其速度。 </li><li>将小鼠在转棒的管当它旋转时5rpm的缓慢稳定的速度。五只小鼠可同时进行测试。 </li><li>一旦开始所有小鼠被放置在运行。内的前15秒的管的速度加速从5-45转之后，它保持该速度。 </li><li>监视运行。运行时间由软件连续记录。运行时会自动停止，当鼠标脱落的管，因为这会激活位于管下方的时间条。重新定位该扭转的管朝向相反的方向，而不停止管旋转运行时，小鼠。 </li><li>结束测试阶段的小鼠都能够运行500秒的持续时间。给小鼠最多两次机会使他们能够改善他们的运行时间，当他们更早掉落。 </li><li>使用的最大运行时间（ 即最长的审判）进行进一步分析。 </li></ol> 4。跑步机练习该跑步机可以用三种方式中的预临床研究的工具。首先，强迫跑步机跑步可以作为本协议中所述加剧疾病的病理（参见： <a href="http://www.treat-nmd.eu/downloads/file/sops/dmd/MDX/DMD_M.2.1.001.pdf" target="_blank">DMD_M2.1.001.pdf</a> ）。其次，小鼠和治疗效果的在此的最大运转能力进行评估（参见让老鼠运行直到用尽该方法<a href="http://www.treat-nmd.eu/downloads/file/sops/dmd/MDX/DMD_M.2.1.003.pdf">DMD_M.2.1.003.pdf</a> ）。最后，跑步机的运行可使用之前的另一个功能测试用尽鼠标，这样它在所述第二测试13执行较差。这是通过如下文所述，之后直接跟随，任一个在协议1-3所描述的功能性测试的锻炼小鼠两次或每周3次进行。 <ol><li>设备设置：上有哪几个老鼠可以茹市售几个跑步机Ñ​​同时且为可抬高，持续时间和速度调整。一些跑步机配有网格提供低强度冲击，以鼓励老鼠跑。然而，mdx小鼠是对应力敏感的，并且可以很容易地通过一个温和的推带的运行方向上的手受到激励以友好的方式。因此，强烈建议不要使用冲击电网。一般来说，刺激手第一次运行会话期间，才需要。 </li><li>将小鼠在水平的跑步机。 </li><li>开始跑步机以12米/分的运行速度。较低的速度（8米/分）在老年小鼠中使用（&gt; 15个月），其中较高的速度容易导致疲劳。 </li><li>在第一次会议上，鼓励老鼠轻轻推他们，当他们靠近皮带的运行结束。 </li><li>当老鼠已经跑了30分钟的时间，将它们放回笼子。 </li><li>重复此每周两次， 例如 12周。 </LI&gt; <li>允许在需要的时候休息时间。例如，一些mdx小鼠必须停止运行，并应允许休息几个分钟。如果发生这种情况，把皮带脱落，给所有小鼠两分钟的休息期，把皮带上两分钟，在4米/分钟。在此之后，增加速度以12米/分钟，并允许小鼠以完成该协议。所有小鼠完成整个运行的协议是很重要的。 注意：如果mdx小鼠需要休息期间，考虑一个热身的30分钟运动方案之前。这种热身阶段组成：一个2分钟适应期在4米/分钟的速度，紧跟着的一个8分钟的热身以8米/分钟。 在我们的手中4-16周龄雌性mdx小鼠都能够完成30分钟运动方案没有休息。也有人报道，在年龄匹配的雄性mdx小鼠的老鼠45％的人需要休息期间，完成练习。热身协议减少停止12 s的量。 </li></ol>

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<li>Massett, M. P., Berk, B. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Strain-dependent+differences+in+responses+to+exercise+training+in+inbred+and+hybrid+mice%5BTitle%5D)+AND+%22Am.+J.+Physiol.+Regul.+Integr.+Comp.+Physiol%22%5BJournal%5D)">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/pubmed?term=((Genetic+variability+in+forced+and+voluntary+endurance+exercise+performance+in+seven+inbred+mouse+strains%5BTitle%5D)+AND+%22J.+Appl.+Physiol%22%5BJournal%5D)">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/pubmed?term=((Physiological+characterization+of+muscle+strength+with+variable+levels+of+dystrophin+restoration+in+mdx+mice+following+local+antisense+therapy%5BTitle%5D)+AND+%22Mol.+Ther%22%5BJournal%5D)">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. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Noninvasive+in+vivo+assessment+of+muscle+impairment+in+the+mdx+mouse+model--a+comparison+of+two+common+wire+hanging+methods+with+two+different+results%5BTitle%5D)+AND+%22J.+Neurosci.+Methods%22%5BJournal%5D)">Noninvasive in vivo assessment of muscle impairment in the mdx mouse model--a comparison of two common wire hanging methods with two different results.</a> J. Neurosci. Methods. 203, 292-297 (2012).</li>
</ol>

作者什么都没有透露。

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><tbody><tr><td>Mouse grip strength meter</td><td>Chatillon DFE (resold by Columbus Instruments)</td><td># 80529</td><td></td></tr><tr><td>Hanging wire 2 limbs device</td><td>Cloth hanger or custom made device</td><td></td><td></td></tr><tr><td>Hanging wire 4 limbs device</td><td>Lid of rat cage or custom made device</td><td></td><td></td></tr><tr><td>Rotarod</td><td>Ugo Basil</td><td># 47600</td><td></td></tr><tr><td>Treadmill for mice Exer 3/6</td><td>Columbus Instruments</td><td># 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

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。

评估在功能性能<em&gt; MDX</em&gt;小鼠模型

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

assessing-functional-performance-in-the-mdx-mouse-model

Research

JoVE Journal

Behavior

Assessing Functional Performance in the Mdx Mouse Model

32.3K 次观看.  Leiden University Medical Center. 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。 

视频: Assessing Functional Performance in the Mdx Mouse Model

Assessment of Sensorimotor Function in Mouse Models of Parkinson's Disease

Sensitive and reliable behavioral outcome measures are essential to the evaluation of potential therapeutic treatments in preclinical trials for many neurodegenerative diseases. In Parkinson's disease, sensorimotor tests sensitive to varying degrees of nigrostriatal dysfunction are fundamental for testing the efficacy of potential therapeutics. Reliable and quite elegant sensorimotor measures exist for rats, however many of these tests measure sensorimotor asymmetry within the rat and are not entirely suitable for the newer genetic mouse models of PD. We have put together a battery of sensorimotor tests inspired by the sensitive tests in rats and adapted for mice. The test battery highlighted in this study is chosen for a) its sensitivity in a wide variety of mouse models of PD, b) its ease in implementing into a study, and c) its low expense. These tests have proven useful in characterizing novel genetic mouse models of PD as well as in testing potential disease-modifying therapies.

In Parkinson's disease and movement disorders in general, sensitive and reliable behavioral assays are essential for testing novel potential therapeutics. Here, we describe a manageable battery of sensorimotor tests for mice that are sensitive to varying degrees of injury to the nigrostriatal system and useful for preclinical studies.

帕金森氏症小鼠模型的感觉功能评估

Sensitive and  reliable behavioral outcome measures are essential to the evaluation of  potential therapeutic treatments in preclinical trials for many  ...

科研

行为学

Measuring the Strength of Mice

Kondziela7 devised the inverted screen test and published it in 1964. It is a test of muscle strength using all four limbs. Most normal mice easily score maximum on this task; it is a quick but insensitive gross screen, and the weights test described in this article will provide a finer measure of muscular strength.
There are also several strain gauge-based pieces of apparatus available commercially that will provide more graded data than the inverted screen test, but their cost may put them beyond the reach of many laboratories which do not specialize in strength testing. Hence in 2000 a cheap and simple apparatus was devised by the author. It consists of a series of chain links of increasing length, attached to a "fur collector" a ball of fine wire mesh sold for preventing limescale build up in hard water areas. An accidental observation revealed that mice could grip these very tightly, so they proved ideal as a grip point for a weight-lifting apparatus. A common fault with commercial strength meters is that the bar or other grip feature is not thin enough for mice to exert a maximum grip. As a general rule, the thinner the wire or bar, the better a mouse can grip with its small claws.
This is a pure test of strength, although as for any test motivational factors could potentially play a role. The use of scale collectors, however, seems to minimize motivational problems as the motivation appears to be very high for most normal young adult mice.

Deficits in muscular strength occur in many clinical conditions such as motor neuron disease. The inverted screen and weight lifting tests described here measure strength in mice almost exclusively, with minimal influence of factors such as coordination.

强度测量小鼠

Kondziela7 devised the inverted screen test and published it in 1964. It is a test of muscle strength using all four limbs. Most normal mice easily score ...

医学

Behavioral and Locomotor Measurements Using an Open Field Activity Monitoring System for Skeletal Muscle Diseases

The open field activity monitoring system comprehensively assesses locomotor and behavioral activity levels of mice. It is a useful tool for assessing locomotive impairment in animal models of neuromuscular disease and efficacy of therapeutic drugs that may improve locomotion and/or muscle function. The open field activity measurement provides a different measure than muscle strength, which is commonly assessed by grip strength measurements. It can also show how drugs may affect other body systems as well when used with additional outcome measures. In addition, measures such as total distance traveled mirror the 6 min walk test, a clinical trial outcome measure. However, open field activity monitoring is also associated with significant challenges: Open field activity measurements vary according to animal strain, age, sex, and circadian rhythm. In addition, room temperature, humidity, lighting, noise, and even odor can affect assessment outcomes. Overall, this manuscript provides a well-tested and standardized open field activity SOP for preclinical trials in animal models of neuromuscular diseases. We provide a discussion of important considerations, typical results, data analysis, and detail the strengths and weaknesses of open field testing. In addition, we provide recommendations for optimal study design when using open field activity in a preclinical trial.

Open field activity levels are used to assess locomotive and behavioral activity levels. This protocol provides a well-designed, standardized protocol to use in preclinical trials for neuromuscular disorders.

行为和运动测量使用一个开放的领域活动监控系统的骨骼肌疾病

The open field activity monitoring system comprehensively assesses locomotor and behavioral activity levels of mice. It is a useful tool for assessing ...

Morris Water Maze Test: Optimization for Mouse Strain and Testing Environment

The Morris water maze (MWM) is a commonly used task to assess hippocampal-dependent spatial learning and memory in transgenic mouse models of disease, including neurocognitive disorders such as Alzheimer&#8217;s disease. However, the background strain of the mouse model used can have a substantial effect on the observed behavioral phenotype, with some strains exhibiting superior learning ability relative to others. To ensure differences between transgene negative and transgene positive mice can be detected, identification of a training procedure sensitive to the background strain is essential. Failure to tailor the MWM protocol to the background strain of the mouse model may lead to under- or over- training, thereby masking group differences in probe trials. Here, a MWM protocol tailored for use with the F1 FVB/N x 129S6 background is described. This is a frequently used background strain to study the age-dependent effects of mutant P301L tau (rTg(TauP301L)4510 mice) on the memory deficits associated with Alzheimer&#8217;s disease. Also described is a strategy to re-optimize, as dictated by the particular testing environment utilized.

This manuscript describes a Morris water maze (MWM) protocol tailored for use with a commonly used mouse model of Alzheimer's disease. The MWM is widely used in transgenic mouse models. Implementation of a procedure sensitive to the background strain of the mouse model is essential for detecting group differences.

Morris水迷宫实验:优化小鼠品系和测试环境

 The Morris water maze (MWM) is a commonly used task to assess hippocampal-dependent spatial learning and memory in transgenic mouse models of disease, ...

Measuring Motor Coordination in Mice

Mice are increasingly being used in behavioral neuroscience, largely replacing rats as the behaviorist's animal of choice. Before aspects of behavior such as emotionality or cognition can be assessed, however, it is vital to determine whether the motor capabilities of e.g. a mutant or lesioned mouse allow such an assessment. Performance on a maze task requiring strength and coordination, such as the Morris water maze, might well be impaired in a mouse by motor, rather than cognitive, impairments, so it is essential to selectively dissect the latter from the former. For example, sensorimotor impairments caused by NMDA antagonists have been shown to impair water maze performance2. 
Motor coordination has traditionally been assessed in mice and rats by the rotarod test, in which the animal is placed on a horizontal rod that rotates about its long axis; the animal must walk forwards to remain upright and not fall off. Both set speed and accelerating versions of the rotarod are available.
The other three tests described in this article (horizontal bar, static rods and parallel bars) all measure coordination on static apparatus. The horizontal bar also requires strength for adequate performance, particularly of the forelimbs as the mouse initially grips the bar just with the front paws. 
Adult rats do not perform well on tests such as the static rods and parallel bars (personal observations); they appear less well coordinated than mice. I have only tested male rats, however, and male mice seem generally less well coordinated than females. Mice appear to have a higher strength:weight ratio than rats; the Latin name, Mus musculus, seems entirely appropriate. The rotarod, the variations of the foot fault test12 or the Catwalk (Noldus)15 apparatus are generally used to assess motor coordination in rats.

Protocols are presented for two established motor coordination tasks, the accelerating rotarod and horizontal bar, also two tests developed in Oxford recently, the static rods and parallel bars. These tests can detect motor impairments potentially of interest in their own right, as well as being possible variables in tests of other areas of behavior.

测量小鼠运动协调

Mice are increasingly being used in behavioral neuroscience, largely replacing rats as the behaviorist's animal of choice. Before aspects of behavior such ...

神经科学

T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice

Forced alternation and left-right discrimination tasks using the T-maze have been widely used to assess working and reference memory, respectively, in rodents. In our laboratory, we evaluated the two types of memory in more than 30 strains of genetically engineered mice using the automated version of this apparatus. Here, we present the modified T-maze apparatus operated by a computer with a video-tracking system and our protocols in a movie format. The T-maze apparatus consists of runways partitioned off by sliding doors that can automatically open downward, each with a start box, a T-shaped alley, two boxes with automatic pellet dispensers at one side of the box, and two L-shaped alleys. Each L-shaped alley is connected to the start box so that mice can return to the start box, which excludes the effects of experimenter handling on mouse behavior. This apparatus also has an advantage that in vivo microdialysis, in vivo electrophysiology, and optogenetics techniques can be performed during T-maze performance because the doors are designed to go down into the floor. In this movie article, we describe T-maze tasks using the automated apparatus and the T-maze performance of &alpha;-CaMKII+/- mice, which are reported to show working memory deficits in the eight-arm radial maze task. Our data indicated that &alpha;-CaMKII+/- mice showed a working memory deficit, but no impairment of reference memory, and are consistent with previous findings using the eight-arm radial maze task, which supports the validity of our protocol. In addition, our data indicate that mutants tended to exhibit reversal learning deficits, suggesting that &alpha;-CaMKII deficiency causes reduced behavioral flexibility. Thus, the T-maze test using the modified automatic apparatus is useful for assessing working and reference memory and behavioral flexibility in mice.

This article presents the protocol of T-maze tests using a modified automated apparatus for assessing the learning and memory functions in mice.

T-迷宫强迫交替和评估工作，并参考在小鼠记忆的左，右的歧视任务

Forced alternation and left-right discrimination tasks using the T-maze have been widely used to assess working and reference memory, respectively, in ...

A Simple and Low-cost Assay for Measuring Ambulation in Mouse Models of Muscular Dystrophy

Measuring functional outcomes in the treatment of muscular dystrophy is an essential aspect of preclinical testing. The assessment of voluntary ambulation in mouse models is a non-invasive and reproducible activity assay that is directly analogous to measures of patient ambulation such as the 6-minute walk test and related mobility scores. Many common methods for testing mouse ambulation speed and distance are based on the open field test, where an animal&#39;s free movement within an arena is measured over time. One major downside to this approach is that commercial software and equipment for high-resolution motion tracking is expensive and may require transferring mice to specialized facilities for testing. Here, we describe a low-cost, video-based system for measuring mouse ambulation that utilizes free and open-source software. Using this protocol, we demonstrate that voluntary ambulation in the dystrophin-null mdx mouse model for Duchenne muscular dystrophy (DMD) is decreased relative to wild-type mouse activity. In mdx mice expressing the utrophin transgene, these activity deficits are not observed and the total distance traveled is indistinguishable from wild-type mice. This method is effective for measuring changes in voluntary ambulation associated with dystrophic pathology, and provides a versatile platform that can be readily adapted to diverse research settings.

This protocol describes a flexible, low-cost system for measuring mouse ambulation in an open field activity assay. We show that a 6-minute ambulation assay based on this system detects a decrease in voluntary movement in mdx mice, and accurately distinguishes improvement in a muscle-specific rescue of these animals.

一种简便、低成本的肌营养不良小鼠步行模型的测定方法

Measuring functional outcomes in the treatment of muscular dystrophy is an essential aspect of preclinical testing. The assessment of voluntary ambulation ...

<meta charset="utf8"></head><body>小鼠模型中自闭症谱系障碍的行为检测

Strategies for Assessing Autistic-Like Behaviors in Mice

Autism spectrum disorder (ASD) is a neurobiologically complex condition with a heterogeneous genetic etiology. Clinically, ASD is diagnosed by social communication impairments and restrictive or repetitive behaviors, such as hand flapping or lining up objects. These behavioral patterns can be reliably observed in mouse models with ASD-linked genetic mutations, making them highly useful tools for studying the underlying cellular and molecular mechanisms in ASD. Understanding how genetic changes affect the neurobiology and behaviors observed in ASD will facilitate the development of novel targeted therapeutic compounds to ameliorate core behavioral impairments. Our lab has employed several protocols encompassing well-described training and testing procedures that reflect a wide range of behavioral deficits related to ASD. Here, we detail two assays to study the core features of ASD in mouse models: self-grooming (a measure of repetitive behavior) and the three-chamber social interaction test (a measure of social interaction approach and preference for social novelty).

<meta charset="utf8"></head><body>评估小鼠自闭症样行为的策略

Rodent models are valuable tools for studying core behaviors related to autism spectrum disorder (ASD). In this article, we expound on two behavioral tests for modeling the core features of ASD in mice: self-grooming, which assesses repetitive behavior, and the three-chamber social interaction test, which documents social impairments.

评估小鼠自闭症样行为的策略

Autism spectrum disorder (ASD) is a neurobiologically complex condition with a heterogeneous genetic etiology. Clinically, ASD is diagnosed by social ...

评估在功能性能

摘要

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