Pathobiology of Aging Mice and GEM: Background Strains and Experimental Design

Pathobiology of Aging Mice and GEM: Background Strains and Experimental Design
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DOI:
10.1177/0300985811430696
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发表时间:
2012-01-01
影响因子:
2.4
通讯作者:
Ward, J. M.
Ward, J. M.
中科院分区:
农林科学2区
文献类型:
--
作者:
Brayton, C. F.;Treuting, P. M.;Ward, J. M.

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使用诱导和自发突变小鼠和基因工程小鼠(及其组合)来研究癌症和其他衰老表型以提高人类功能寿命将涉及对衰老小鼠的研究。遗传背景影响病理表型、死亡原因以及寿命。提高对预期表型、影响表型和研究结果的实验​​变量以及实验设计选项和原理的认识,可以最大限度地利用基因工程小鼠 (GEM) 模型在衰老转化研究中的效用。本综述旨在提供资源,以加强涉及 GEM 的慢性和长寿研究的设计和实践。 C57BL6、129 和 FVB/N 菌株受到重视,因为它们广泛用于产生敲除、转基因和条件突变体 GEM。还包括其他近交系家族的病理学资源,包括 A、AKR、BALB/c、C3H、C57L、C58、CBA、DBA、GR、NOD.scid、SAMP 和 SJL/J,以及非近交系小鼠,包括 4WC、AB6F1、Ames dwarf、B6、129、B6C3F1、BALB/c,129、 Het3、nude、SENCAR 和几支瑞士股票。比较和讨论了长期横断面和纵向研究的实验策略,以评估死亡原因或促成因素、疾病负担、病理表型谱、寿命和功能健康寿命(健康跨度)。
The use of induced and spontaneous mutant mice and genetically engineered mice (and combinations thereof) to study cancers and other aging phenotypes to advance improved functional human life spans will involve studies of aging mice. Genetic background contributes to pathology phenotypes and to causes of death as well as to longevity. Increased recognition of expected phenotypes, experimental variables that influence phenotypes and research outcomes, and experimental design options and rationales can maximize the utility of genetically engineered mice (GEM) models to translational research on aging. This review aims to provide resources to enhance the design and practice of chronic and longevity studies involving GEM. C57BL6, 129, and FVB/N strains are emphasized because of their widespread use in the generation of knockout, transgenic, and conditional mutant GEM. Resources are included also for pathology of other inbred strain families, including A, AKR, BALB/c, C3H, C57L, C58, CBA, DBA, GR, NOD.scid, SAMP, and SJL/J, and non-inbred mice, including 4WC, AB6F1, Ames dwarf, B6, 129, B6C3F1, BALB/c,129, Het3, nude, SENCAR, and several Swiss stocks. Experimental strategies for long-term cross-sectional and longitudinal studies to assess causes of or contributors to death, disease burden, spectrum of pathology phenotypes, longevity, and functional healthy life spans (health spans) are compared and discussed.