Mouse models of Huntington disease: variations on a theme
Mouse models of Huntington disease: variations on a theme
复制标题
DOI：
10.1242/dmm.002451
复制
发表时间：
2009-03-01
影响因子：
4.3
通讯作者：
Hayden, Michael R.
中科院分区：
文献类型：
--
作者：
Ehrnhoefer, Dagmar E.;Butland, Stefanie L.;Hayden, Michael R.
在人类中进行化合物临床试验的一个公认的先决条件是在动物模型中成功缓解疾病。然而，对于某些疾病，将药物作用从小鼠模型成功转化到临床的效果有限。一个问题是当前的模型是否能够准确地再现人类疾病。在这里，我们研究了可用于亨廷顿病（HD）治疗测试的小鼠模型，亨廷顿病是一种迟发性神经退行性疾病，目前尚无有效的治疗方法。目前的小鼠模型与人类状况有不同程度的相似性。在表达截短或全长人类或全长小鼠突变亨廷顿蛋白 (mHTT) 的小鼠模型中观察到显着的表型差异。表型表达的这些差异可能归因于蛋白质背景、小鼠品系的影响以及小鼠 Htt 和人类 HTT 基因之间调控序列的差异。
An accepted prerequisite for clinical trials of a compound in humans is the successful alleviation of the disease in animal models. For some-diseases, however, successful translation of drug-effects from mouse models to the bedside has been limited. One question is whether the current models accurately reproduce the human disease. Here, we examine the Mouse models that are available for therapeutic testing in Huntington disease (HD), a late-onset neurodegenerative disorder for which there is no effective treatment. The current mouse models show different degrees of similarity to the human condition. Significant phenotypic differences are seen in mouse models that express either truncated or full-length human, or full-length mouse, mutant huntingtin (mHTT). These differences in phenotypic expression may be attributable to the influences of protein context, mouse strain and a difference in regulatory sequences between the mouse Htt and human HTT genes.