Reverse-translational biomarker validation of Abnormal Repetitive Behaviors in mice: an illustration of the 4P's modeling approach.
Reverse-translational biomarker validation of Abnormal Repetitive Behaviors in mice: an illustration of the 4P's modeling approach.
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DOI：
10.1016/j.bbr.2011.01.002
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发表时间：
2011-06-01
影响因子：
2.7
通讯作者：
Mench, Joy A.
中科院分区：
文献类型：
--
作者：
Garner, Joseph P.;Thogerson, Collette M.;Dufour, Brett D.;Wuerbel, Hanno;Murray, James D.;Mench, Joy A.
关键词：
NIMH的新战略计划强调“4P”(预测、先发制人、个性化和种群)和基于生物标记物的医学，要求动物建模方法发生根本性转变。特别是，4P的模型将是非决定性的(即疾病的严重程度将取决于次级环境和遗传因素)；并通过将动物同源物反向翻译为人类生物标记物来验证。生物标记物方法的一个强大后果是，不同密切相关的疾病具有独特的生物标记物指纹。通过匹配这一“指纹”，动物可以被验证为单一疾病的高度特异性模型；或者通过匹配共同的生物标记物，动物可以被验证为多个疾病中出现的症状的模型。在这里，我们用小鼠的两种异常重复行为(ARB)来说明这一方法：刻板印象和理发(拔头发)。我们开发了区分人类ARB的神经心理学生物标记物的动物版本，并测试了不同小鼠ARB的指纹。正如预测的那样，这两个小鼠ARB与不同的生物标记物相关。理发和刻板印象都可以被认为是强迫症的模型(尽管它们被广泛使用)，因为缺乏边缘生物标记物，这是强迫症的特征，因此是有效模型所必需的。相反，理发与毛发狂症的指纹相匹配(即选择性移位缺陷)，这表明这可能是这种疾病的高度特异性模型。相比之下，刻板印象只与多种疾病中刻板印象相关的生物标记物(反应转换缺陷)相关，这表明动物刻板印象在多种障碍中模拟刻板印象。
The NIMH's new strategic plan, with its emphasis on the “4P's” (Prediction, Preemption, Personalization, & Populations) and biomarker-based medicine requires a radical shift in animal modeling methodology. In particular 4P's models will be non-determinant (i.e. disease severity will depend on secondary environmental and genetic factors); and validated by reverse-translation of animal homologues to human biomarkers. A powerful consequence of the biomarker approach is that different closely-related disorders have a unique fingerprint of biomarkers. Animals can be validated as a highly-specific model of a single disorder by matching this `fingerprint'; or as a model of a symptom seen in multiple disorders by matching common biomarkers. Here we illustrate this approach with two Abnormal Repetitive Behaviors (ARBs) in mice: stereotypies; and barbering (hair pulling). We developed animal versions of the neuropsychological biomarkers that distinguish human ARBs, and tested the fingerprint of the different mouse ARBs. As predicted, the two mouse ARBs were associated with different biomarkers. Both barbering and stereotypy could be discounted as models of OCD (even though they are widely used as such), due to the absence of limbic biomarkers which are characteristic of OCD and hence are necessary for a valid model. Conversely barbering matched the fingerprint of trichotillomania (i.e. selective deficits in set-shifting), suggesting it may be a highly specific model of this disorder. In contrast stereotypies were correlated only with a biomarker (deficits in response shifting) correlated with stereotypies in multiple disorders, suggesting that animal stereotypies model stereotypies in multiple disorders.
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影响因子：
3.4
作者：
Caldwell, Gary W.;Ritchie, David M.;Yan, Zhengyin
通讯作者：
Yan, Zhengyin
DOI：
10.1079/9780851990040.0121
发表时间：
2006-01-01
期刊：
STEREOTYPIC ANIMAL BEHAVIOUR: FUNDAMENTALS AND APPLICATIONS TO WELFARE, 2ND EDIITON
影响因子：
--
作者：
Garner, J. P.
通讯作者：
Garner, J. P.
影响因子：
4.1
作者：
Bohne, A;Keuthen, NJ;Wilhelm, S
通讯作者：
Wilhelm, S
影响因子：
6.9
作者：
FRITH, CD;DONE, DJ
通讯作者：
DONE, DJ
DOI：
10.1523/jneurosci.2820-08.2008
发表时间：
2008-10-29
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bissonette GB;Martins GJ;Franz TM;Harper ES;Schoenbaum G;Powell EM
通讯作者：
Powell EM