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表观遗传学研究中的动物模型:实验动物管理与使用委员会对整个生命周期的考量

Animal models in epigenetic research: institutional animal care and use committee considerations across the lifespan.

作者信息

Harris Craig

机构信息

Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109-2029, USA.

出版信息

ILAR J. 2012;53(3-4):370-6. doi: 10.1093/ilar.53.3-4.370.

Abstract

The rapid expansion and evolution of epigenetics as a core scientific discipline have raised new questions about how endogenous and environmental factors can inform the mechanisms through which biological form and function are regulated. Existing and proposed animal models used for epigenetic research have targeted a myriad of health and disease endpoints that may be acute, chronic, and transgenerational in nature. Initiating events and outcomes may extend across the entire lifespan to elicit unanticipated phenotypes that are of particular concern to institutional animal care and use committees (IACUCs). The dynamics and plasticity of epigenetic mechanisms produce effects and consequences that are manifest differentially within discreet spatial and temporal contexts, including prenatal development, stem cells, assisted reproductive technologies, production of sexual dimorphisms, senescence, and others. Many dietary and nutritional interventions have also been shown to have a significant impact on biological functions and disease susceptibilities through altered epigenetic programming. The environmental, chemical, toxic, therapeutic, and psychosocial stressors used in animal studies to elicit epigenetic changes can become extreme and should raise IACUC concerns for the well-being and proper care of all research animals involved. Epigenetics research is rapidly becoming an integral part of the search for mechanisms in every major area of biomedical and behavioral research and will foster the continued development of new animal models. From the IACUC perspective, care must be taken to acknowledge the particular needs and concerns created by superimposition of epigenetic mechanisms over diverse fields of investigation to ensure the proper care and use of animals without impeding scientific progress.

摘要

表观遗传学作为一门核心科学学科的迅速发展和演变,引发了关于内源性和环境因素如何影响生物形态和功能调控机制的新问题。现有的以及提议用于表观遗传学研究的动物模型针对了无数健康和疾病终点,这些终点在性质上可能是急性、慢性和跨代的。起始事件和结果可能贯穿整个生命周期,引发机构动物护理和使用委员会(IACUCs)特别关注的意外表型。表观遗传机制的动态性和可塑性产生的效应和后果,在不同的空间和时间背景下,包括产前发育、干细胞、辅助生殖技术、性二态性的产生、衰老等,会有不同的表现。许多饮食和营养干预也已被证明通过改变表观遗传编程对生物功能和疾病易感性有重大影响。在动物研究中用于引发表观遗传变化的环境、化学、有毒、治疗和心理社会应激源可能会变得极端,这应该引起IACUCs对所有涉及的研究动物的福祉和妥善护理的关注。表观遗传学研究正迅速成为生物医学和行为研究各个主要领域寻找机制的一个组成部分,并将促进新动物模型的持续发展。从IACUC的角度来看,必须注意认识到表观遗传机制叠加在不同研究领域所带来的特殊需求和问题,以确保在不妨碍科学进展情况下对动物进行妥善护理和使用。

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